Background: Except for some information on relative frequencies of different cancers in selected areas, the epidemiology of cancer in Cameroon is relatively unknown. Though there is no reliable data on its incidence and pattern, with an estimated 15,000 new cases diagnosed annually and a prevalence of about 25.000 cases throughout the country, cancer is being increasingly recognized as a public health problem in Cameroon. The Yaounde Cancer Registry is a population registry physically located at the General Hospital Yaounde that has been operating since 2004. It collects data from about 20 sources that cover the entire population of Yaounde estimated in 2010 at about 1,299,369. Objectives: The objective of this study was to find out the incidence and trends of cancer in the Yaounde population in the period 2004–2006/2010–2011. It is hoped that this will enable policy makers, health providers and other stake holders plan appropriate health management policy in this population. Materials and Methods: This report presents the cancer incidence for 5 years, 2004–2006/2010–2011 in the Yaounde population estimated at 1,299,369. Data of the Yaounde Cancer Registry was reviewed for the period under study using Canreg5 software. Only malignant cases registered during the period under study were used in the analysis while benign and other uncertain tumours were excluded. The 2010 census estimates by the National Institute of Statistics was employed to calculate the incidence, age-standardized and crude rates. Other software like excel, epi info were also used for analysis. Survival studies were not carried out in this study. Results: A total of 4,689 new malignant cases were reported, of which 2,901 (68%) were females and 1,788 (32%) were males. The incidence showed an average of 358 for men and 580 for women. The average age of cancer patients in Yaounde is 44.8 years. Morphologically confirmed cases accounted for 89% .The annual number of cases varied from 970 in 2004 to 784 in 2011. There is a persistent relative increase in HIV-related malignancies (Non Hodgkin lymphoma and Kaposi sarcoma) and colorectal cancers in both sexes. The overall Age Standardized Incidence Rate (ASR) for all cancers during the period was 44.35 per 100, 000 in males and 62.35 in females. The commonest cancers found in the population were breast (18.5%), cervix (13.8%), Non-Hodgkin lymphoma (11.9%), prostate (7.3%), Kaposi sarcoma (6.9%), liver (2.9%), colorectal (2.9%), soft tissue (2.8%), ovary (2.4%) and skin (2.3%). Conclusion: Cancer is a public health problem in Cameroon. HIV-associated and colorectal cancers are emerging cancers in this community. This calls for more population-based cancer registries in the country to provide reliable information on cancer incidence in different localities while cancer and cancer-related deaths should be made compulsorily reportable if proper monitoring is to be achieved.