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The objective was to study the time trends in site-specific oral cancer incidence and to determine the age-and socio-economic profile over time in Karachi South. Oral cancer ranks second in this population, in both genders. The incidence is the highest reported worldwide. Incident oral cancer cases received at the Karachi Cancer Registry during 1(st) January 1995 to 30(th) June 2004 were reviewed. To ensure maximally complete data, cases registered between 1(st) January 1995 and 31(st) December 2002 were considered for the present study. Cases of lymphoma, leukemia and melanoma were not included. Trends were studied by grouping cases into two periods, 1995-1997 and 1998-2002. A total of 2253 cases of oral cancer were registered in Karachi South for the 8 year study period accounting for 8.8% of all cancer cases. Overall, the most common site was the mucosa cheek (55.9%), followed by the tongue (28.4%), palate (6.8%), gum (4.4%), lip (3.1%) and floor of the mouth (1.4%). About 30% of cases occurred in patients 40 years and younger and 23% occurred in patients 65 years and older. Sub-categories of oral cancer showed variation in trends, but an earlier onset of disease in period two was evident for all categories. The incidence of lip cancer in men decreased, the rates remained level in females. An increased incidence was observed for tongue, but a more dramatic increase in the cheek was evident in both sexes, despite no improvement during the past decade in detection of early, localized lesions. A strong socio-economic factor with a poorer, low literacy profile of oral cancer was apparent in the entire study period. The evidence that the largest increase in incidence has occurred in this population may unfavorably affect the mortality rates. Oral cancer trends are an interplay of prevalent risk factors, the level of prevalence, preventive education and intervention. Cost effective and efficient cancer control focused around the target populations would be beneficial for Pakistan. Educational campaigns should include information on oral hygiene, awareness of risk factors and symptoms and the importance of seeking early professional help when any of these are recognized. Audio-visual media involvement is imperative in view of the literacy status of the target population. Capacity building is required by the Government to increase the availability and accessibility of professionals. Population screening would reduce the incidence of oral cancer, but requires careful planning, and extensive financial resources. Mobilization of general practitioners, health visitors, volunteer organizations and medical students for early detection of oral cancer is the essential need of today.