Objective: Τhe study aimed to study the rate of atypical squamous cells of undetermined significance (ASCUS) that progressed to high-grade squamous intraepithelial lesions (HGSIL), as well as the number of patients who finally necessitated a surgical intervention during follow-up. Methods: A prospective study was conducted on patients admitted for colposcopy during 2007-2012. We exclusively included those who presented with newly ASCUS diagnosis, while patients with a history of cervical intraepithelial neoplasia (CIN) were excluded. Primary end points were the cumulative rate of HGSIL during follow-up and the rate of surgical procedures performed because of such lesions. Results: There were 134 ASCUS cases included. Overall, there were 48 (35.8%) surgical excision procedures performed to treat or eliminate HGSIL during the follow-up period. According to the final histopathology of surgical specimens, the cumulative rate of CIN2 or higher cervical lesions was 28.4% (n = 38). Conclusion: The cumulative rate of CIN2+ during follow-up period was almost 30% for patients with ASCUS, with the necessity for interventional treatment being even higher.