"I was traipsing through the garment district trying to get a job and my husband kept urging me to open my own business, " she told a writer for WWD. "I hated the garment district. And after one too many disappointments, I approached Mary Ann with the idea of a collection."

The pair called their new line Robespierre, after a notorious figure in the French Revolution, and in August of 1987 they opened a small retail space in New York City's East Village, which was a rough neighborhood at the time and known for its illicit-drug trade. "The rent was $500, " Lepore admitted in the Columbus Dispatch article. "It was not an ideal location." The 400-square-foot store featured designs by Lepore and Vassilakos that were essentially vintage looks updated for the punk-rock crowd, such as pompom skirts and smoking jackets. Within a year, Lepore and her partner decided to close the store and concentrate on their wholesale business instead, which seemed promising after posh clothing retailer Barneys New York placed an order. More than 50 other stores across the United States were also interested in carrying Robespierre, but Lepore's second collection did not fare as well, and the business tanked. She had financed the manufacturing costs with the help of a loan from her parents. "My father mortgaged the house, and I lost it, " she told Hood in the Columbus Dispatch. "Within three years[the money] was gone. I had to work five years to get it back."

By the mid-1990s, Lepore was on her own, and staying afloat by putting out eminently wearable, feminine items that were priced in the moderate bridge sportswear category. She opened a new space in Manhattan in 1996, and dropped the Robespierre moniker in favor of her own name on the label. After adding a dress line, she began showing her fall/ winter and spring/summer collections during New York Fashion Week, the twice-yearly event held in Bryant Park in which designers present their newest wares to store buyers and the press. It was a major expense, but by 2000 her SoHo boutique was doing well enough to help defray the staging costs. "You definitely benefit from doing the shows, " she told WWD 's Lauren DeCarlo. "It pushes you to experiment with more newness; otherwise, you get comfortable. The shows help you push the envelope. It's crazy, and I complain about it for three months, but it's worth it in the end."

By 2003, Lepore had also opened a retail space in Los Angeles, and entertainment-industry insiders began to clamor for her clothes to use on screen. She dressed Reese Witherspoon in the 2003 comedy Legally Blonde 2 , and Lepore's designs also appeared regularly on Sarah Jessica Parker on the hit HBO series Sex and the City. One outfit not listed on the series' fashion-credits page was the rainbow-hued dress that Parker's Carrie Bradshaw wore when she fell into the water at a lakefront eatery in New York City's Central Park. There was a rush of viewer interest in it, but it was a one-off, Lepore told the New York Post. "It was so sad, because everyone on the planet wanted that dress, " she lamented. "But we couldn't make it because the fabric was printed really crooked, and we couldn't find a manufacturer."

Lepore's business had grown steadily over the decade. With items priced from $45 to $400 at retail, her company managed to do a respectable $63 million in estimated sales for 2005. In 2006, she launched fragrance and footwear lines, and had stores in Boston, London, Las Vegas, and even Tokyo. Her husband serves as president of her company, while her Ohio family are still her most enthusiastic supporters. "I couldn't be more proud of Nanette, " her mother, Jeannie, told Cleveland Plain Dealer fashion columnist Kim Crow while visiting backstage at Lepore's Spring 2006 collection. "I never put it together at the time, but she was always taking cutouts and making clothes for her paper dolls. I never guessed it would lead to this." In turn, Lepore credits much of her success to her family, which includes her sister, Michelle Hagan, the wife of Youngstown's mayor. "I have to be able to stare in the mirror and know it's going to be great, " she told Crow about her creative process. "I always think about how it's going to look on my family, my friends, not just the models."