In 2009, the first National Population-based Cancer Registry (NCR) was established in Sudan. We report in this study, the first data from the NCR for Khartoum State for the period 2009–2010. The NCR staff used passive and active approaches to collect data on cancer diagnosed by all means in Khartoum State. Rates were age standardized to the 2010 Sudan Standard Population and 1966 and 2000 World Standard Population and expressed per 100,000 populations. During 2009–2010, 6771 new cancer cases were registered. Of those, 3646 (53.8%) cases were in women and 3125 (46.2%) were in men. The most commonly diagnosed cancer among women was breast followed by leukemia, cervix, and ovary, and among men it was prostate cancer followed by leukemia, lymphoma, oral, colorectal, and liver. In children less than 15 years of age, leukemia was the most common cancer followed lymphoma, and cancer of the eye, bone, kidney, and the brain. The overall age-standardized rate (ASR) per 100,000 population was higher in women (124.3) than in men (90.8) using 2010 Sudan Standard Population. Similarly, it was higher in women (188.6 and 206.3 per 100,000 population) than in men (145.4 and 160.0 per 100,000 population) using 1966 and 2000 World Standard Population, respectively. The data from NCR indicated that prostate and breast as the most commonly diagnosed cancer sites in men and women in Khartoum, while cancer of the cervix trailed behind portraying a cancer picture similar to that of the developed world. Despite the study limitations, the NCR data gave a fair representation of cancer profile of Khartoum State and underscored the need for high-quality cancer registries in Sudan.