Pironkova made a solid start to 2008, winning two qualifying matches at the Tier-II event in Sydney before bowing out in three sets to Dominika Cibulková. She reached the second round of the Australian Open, losing to second-seeded Svetlana Kuznetsova in straight sets. Pironkova caused another upset at the Rome Masters, when as a qualifier, she beat top seed and world No. 3, Ana Ivanovic, in the second round for the biggest victory of her career at that time. Pironkova advanced to the quarterfinals, her first ever at a Tier-I event, when Victoria Azarenka retired during their third round match with Pironkova leading, but, was defeated in three sets by Anna Chakvetadze. In September, Pironkova reached the final of an ITF event in Sofia, where she lost to Nuria Llagostera Vives. Pironkova ended the year ranked No. 46 in the world, marking her first ever top-50 season.