The c-myc oncogene status was determined in patients with nondysplasia (ND; 9 patients), low-grade squamous intraepithelial lesion (LGSIL; 12 patients), high-grade squamous intraepithelial lesion (HGSIL; 21 patients) and invasive squamous cell carcinoma (ISCC; 20 patients) of uterine cervix using fluorescent quantitative polymerase chain reaction (PCR). In the same paraffin-embedded specimens, other potential risk factors were also screened: human papillomavirus (HPV) infection, Ha-ras codon 12 mutation, DNA aneuploidy. Gene amplification, identified as c-myc copy numbers greater than the mean value +2 SD of patients with ND, was seen in 44% patients with LGSIL, 76% patients with HGSIL, and 67% patients with ISCC. These data indicate that c-myc amplification is one of the critical early events in the progression of uterine cervical lesions. HPV infection of various subtypes was identified in 0% patients with ND, 55% patients with LGSIL, 95% patients with HGSIL, and 84% patients with ISCC. No codon 12 mutation of the Ha-ras gene was found in this series. Aneuploid DNA pattern was seen in 0% patients with ND, 58% patients with LGSIL, 90% patients with HGSIL, and 80% patients with ISCC. There was a significant correlation between HPV infection and DNA aneuploidy. However, no relationship was seen between c-myc status and other factors in this series. Patients with HGSIL and ISCC almost always (95%) had multiple risk factors, whereas more than half of the patients with LGSIL had no or only one risk factor (P = 0.0001).