Purpose Noncommunicable diseases, prominently cancer, have become the second leading cause of death in the adult population of Ethiopia. A population-based cancer registry has been used in Addis Ababa (the capital city) since 2011. Availability of up-to-date estimates on cancer incidence is important in guiding the national cancer control program in Ethiopia. Methods We obtained primary data on 8,539 patients from the Addis Ababa population-based cancer registry and supplemented by data on 1,648 cancer cases collected from six Ethiopian regions. We estimated the number of the commonest forms of cancer diagnosed among males and females in Ethiopia and computed crude and age-standardized incidence rates. Results For 2015 in Ethiopia, we estimated that 21,563 (95% CI, 17,416 to 25,660) and 42,722 (95% CI, 37,412 to 48,040) incident cancer cases were diagnosed in males and females, respectively. The most common adult cancers were: cancers of the breast and cervix, colorectal cancer, non-Hodgkin lymphoma, leukemia, and cancers of the prostate, thyroid, lung, stomach, and liver. Leukemia was the leading cancer diagnosis in the pediatric age group (age 0 to 14 years). Breast cancer was by far the commonest cancer, constituting 33% of the cancers in women and 23% of all cancers identified from the Addis Ababa cancer registry. It was also the commonest cancer in four of the six Ethiopian regions included in the analysis. Colorectal cancer and non-Hodgkin lymphoma were the commonest malignancies in men. Conclusion Cancer, and more prominently breast cancer, poses a substantial public health threat in Ethiopia. The fight against cancer calls for expansion of population-based registry sites to improve quantifying the cancer burden in Ethiopia and requires both increased investment and application of existing cancer control knowledge across all segments of the Ethiopian population.