ObjectiveThe objective of this report is to provide an overview of lip and oral cavity cancer in Karachi, the largest city in Pakistan. MethodsThis study was undertaken at the Dow Cancer Registry. During 2010–2019, all patients who were residents of Karachi who had been diagnosed with lip and oral cavity cancer were registered and recruited for this study. The data were entered in SPSS and MS Excel sheets to investigate frequencies, age-standardized-rates (ASR) and other clinicopathological parameters. The data from our study were compared with the ASR of lip and oral cavity cancer from selected Asian countries. ResultsDuring the defined period, 22,858 cancer cases were registered. Of these, 4,400 (19.2%, ASR 28.0) were lip and oral cavity cancer (the most common type found in males and the second most common type in females), of which 2,986 (67.8%) were found in males, while 1,414 (32.1%) were reported in females. Squamous cell carcinoma was the most common type (97.7%). Most tumours were moderately differentiated (67.7%) followed by poorly (16.6%), and well differentiated (15.7%). ConclusionWe report an alarmingly high ASR of lip and oral cavity cancer in Karachi as compared to Pakistan as a whole and other Asian countries.