There are few cancer trend data reported in sub-Saharan Africa notably due to the scarcity of population-based cancer registries (PBCRs). The Eastern Cape Province PBCR is amongst the few registries in sub-Saharan Africa that reports data for a rural population. Trends in cancer incidence are reported for the period 1998-2012. Registered cases, age-standardized rates (ASRs) and standardized rate ratios are presented for the most common cancers in both males and females in three periods (1998-2002, 2003-2007 and 2008-2012). In males, the most commonly diagnosed cancer during the 15 year period was cancer of the oesophagus; incidence rates showed a significant decline over the 15 year period, entirely due to a 30% decrease between 2003-2007 and 2008-2012, to an ASR of 23.2 per 100,000 population. This was followed by prostate cancer, the incidence of which was more than doubled to a level of 9.9/100,000. In women, cancer of the cervix uteri has become the most common malignancy, with a significant increase in incidence during the period to 29.0/100,000. Oesophageal cancer is second in frequency, with (as in males) a significant decline in the final 10 years to an incidence of 14.5/100,000 in 2008-2012. The incidence of breast cancer increased by 61%, although the absolute rate remains low (12.2/100,000). The incidence rates of colorectal cancer are low, and the increases in incidence, although relatively large (35% in men, 63% in women) were not statistically significant. Kaposi sarcoma showed a dramatic increase in incidence in both sexes (3.5-fold in men, 11-fold in women) although the incidence remains relatively low by southern African standards. Cancer prevention and control activities in the area need to be informed by these data and strengthened.