Background: Cancer is emerging as a major cause of morbidity and mortality in low and middle-income countries. Cancer registry figures help for planning and delivery of health services. This paper provided the first results of cancer incidence and mortality [Crude (CR) and age-standardized (ASR)] rates (world-standard population) of Trivandrum district, South India and compared with other registries under the network of National Cancer Registry Programme (NCRP), Government of India. Materials and Methods: Trivandrum district cancer registry encompasses a population of 3.3 million, compiles data from nearly 75 sources (hospitals and diagnostic laboratories) and included under the NCRP in 2012. During 2012-2014, registry recorded 15,649 incident cases and 5667 deaths. Proportion of microscopic diagnosis was 85% and ‘Death certificate only’ was 8%. Results: Total cancer incidence (CRs) rates were 161 and 154 (ASR: 142.2 and 126) and mortality rates were 66 and 49 (ASR: 54 and 37) per 105 males and females respectively. Common cancers in males were lung (ASR:19), oral cavity (ASR:15), colo-rectum (ASR:11.2), prostate (ASR:10.2) and lymphoma (ASR:7) and in females, breast (ASR:36), thyroid (ASR:13.4), cervix-uteri (ASR:7.3), ovary (ASR:7) and colo-rectum (ASR:7). Nationally, the highest CRs for breast, prostate, colo-rectum, corpus-uteri and urinary bladder cancers and low incidence of cervix-uteri cancer were observed in Trivandrum. Conclusion: Cancer incidence (CR) in Trivandrum was the highest in both genders in India (except Aizwal). This is mainly due to the highest lifeexpectancy in Kerala. Also, an epidemiologic transition in cancer pattern is taking place and is changing to more similar to “western” jurisdictions.