Uterine cervix cancer is an important public health problem in developing countries. However, there is a substantial lack of inter-observer diagnostic reproducibility for its precursor lesions (CIN1). The study was performed to evaluate the usefulness of p16(INK4A) overexpression as a surrogate marker for uterine cervix precancerous lesions and high-risk human papillomavirus (HPV) infection. We conducted a retrospective study of 87 uterine cervix specimens, including 7 normal tissue samples, 17 benign lesions, 34 precancerous lesions, 22 invasive squamous cell carcinomas (SCC), and 7 adenocarcinomas. Immunohistochemistry was used to find p16(INK4A) overexpression. HPV infection was detected by PCR. No immunoreactivity for p16(INK4A) was detected in normal tissue or benign lesions. p16(INK4A) immunoreactivity was focal in CIN1, whereas strong and diffuse immunoreactivity for p16(INK4A) was uniformly observed in both the nucleus and the cytoplasm of all CIN2 and 3, as well as in those of invasive SCC and adenocarcinomas. A statistically significant association was observed between p16(INK4A) overexpression, lesion grade, and high-risk HPV infection (p<0.0001). p16(INK4A) overexpression is a useful additional marker for the interpretation of problematic uterine cervical lesions and can help to reduce the variability during evaluation of suspicious biopsies of the uterine cervix.