The previous studies of p16^INK4a, pRb, p53, and Ki-67 expression suggested that these markers may be preferentially expressed in cervical neoplasms. The purpose of this study was to assess the expression and the clinical significance of p16^INK4a, pRb, p53, and Ki-67 proteins in cervical lesions. We obtained 106 cases with various categories of cervical squamous mucosa, including squamous cell carcinoma (n=35), cervical intraepithelial neoplasia (CIN) II/III (n=26), CIN I (n=10), squamous metaplasia (n=15), and normal squamous mucosa (n=20). Immunohistochemical staining was performed for p16INK4a, pRb, p53, and Ki-67 proteins in formalin-fixed and paraffin-embedded tissue sections of the uterine cervix. Evaluation of immunohistochemical staining was based on the frequencies of expression and the mean immunoreactivity scores (IS) in each diagnostic category. p16INK4a positive sotaining was observed in 26 of 35 cases (74.3%) of squamous cell carcinoma, in 16 of 26 cases (61.5%) of CIN II/III, in six of 10 cases (60%) of CIN I, in nine of 15 cases (60%) of squamous metaplasia, and negative in normal squamous mucosa. pRb expression was detected in all diagnostic categories; however, the proportion of pRb positive cells was relatively decreased in CIN II/III (38.5%) and squamous cell carcinomas (51.4%), compared to normal squamous epithelium (90%) and squamous metaplasia (73.3%). No significant differences in expression of p53 were observed in any diagnostic categories. Ki-67 expression was increased in squamous cell carcinoma (37.1%), CIN II/ III (42.3%), and CIN I (40%), but negative in squamous metaplasia and normal mucosa. In 35 cases of squamous cell carcinomas, multivariate analysis revealed no differences in p^INK4a, pRb, p53, and Ki-67 expression according to the age of the patient, lymph node metastasis and clinical stage. In conclusion, the combined use of p16^INK4a and Ki-67 immunoreactivity could improve the diagnostic specificity of squamous cell carcinoma of the uterine cervix.