Regardless of the fact that cancers of GI tract have been reported to be the most common fatal neoplasms in East Azerbaijan, there is a serious lack of population-based studies in this region. A comprehensive search was therefore undertaken to prospectively register all cases of cancer occurring in the province during March 2006-2007. Diagnosis of cancer was based on histopathology of primary lesions in 84.0% of cases, clinical investigation and ultrasound in 7.2%, only clinical investigation in 5.4%, and histology of metastasis in 2.9. Less than 1% were based on cytology and death certificates in one official year. A total of 4,922 cancers (mean age 60.2+18.13 years) were diagnosed during this population-based study. Of these, 56.8% (2114) were in males. ASRs for all cancers in males and females were 164.3 and 130.6 respectively. The top five sites for cancer in males (excluding skin cancer) according to the calculated ASR (world) were stomach (26.0), bladder (15.7), esophagus (12.4), colon and rectum (11.6) and blood (10.8); in females, they were breast (23.5), esophagus (11.7), stomach (11.6), colon and rectum (9.7) and nervous system (5.5). This first comprehensive report on cancer incidence in East Azerbaijan, documents particularly high incidence rates for esophageal and gastric cancer across the sexes.