Objective. To establish the time trends of the frequency and prevalence of oral cavity cancer in regard to age and gender in a 20-years (time period 1989 ? 2008) cohort of Mexicans. Design and Setting. 13,235 head and neck biopsies from the archive of the Oral Pathology Laboratory, Dental School, National Autonomous University of Mexico were revised. The cases with diagnoses of oral cancer were selected. Gender and age at diagnosis was obtained from medical records. The frequency and prevalence of oral cavity cancer and oral squamous cell carcinoma were assessed biannually in regard to the total number of population served by the oral pathology laboratory. The statistical significance of trends was established using the linear logistic regression (curve estimation) test (s 0.05). Results. 298 cases (138 males; 160 females) of oral cancer were included; 167 (92 females; 75 males; female:male ratio: 1.1:1) corresponded to oral squamous cell carcinoma. From 1989 to 2008 the prevalence of oral cancer and oral squamous cell carcinoma increased 200% (s 0.05) and 100% (s 0.000) respectively. The increase of frequency and prevalence was observed in both genders however only in females was significant (s 0.000). We do not identify changes in the age at diagnosis. Conclusions. Oral cancer, specifically oral squamous cell carcinoma, has increase in Mexicans females in the last 20 years.