The provincial health authority reported a high mortality rate from upper GI cancer in the newly established Ardabil Province of northwest Iran. A comprehensive search was undertaken to survey and register all cases of cancer during a 4-year (1996–1999) period among the indigenous population of Ardabil Province, including subjects seeking care in the cities of Tabriz and Tehran. Diagnosis of cancer was based on histopathology in 71.4%, clinical or radiologic findings in 25% and death certificate in 3.6% of cases. A total of 3,455 cancers (mean age 57.1 ± 17.3 years) was found during the study. Of these, 60% (2,072) were in males. ASRs for all cancers in males and females were 132.0 and 96.3, respectively. The top 5 cancers in males (excluding skin cancer) according to the calculated ASR were stomach (25.4), esophagus (15.4), lung and bronchus (7.9), colon and rectum (7.9) and bladder (7.6); in females, these were stomach (25.42), esophagus (14.4), breast (7.6), colon and rectum (5. 9) and lung and bronchus (3.6). Compared to rates obtained 30 years ago, the incidence of upper GI cancer in this region has increased about 100%, and there is a striking increase in the incidence of gastric cancer with a decline in the esophageal cancer rate. ASRs for gastric cancer in Ardabil were 49.1 for males and 25.4 for females, while for esophageal cancer these were 15.4 and 14.4, respectively. The ASR for cervical cancer was the lowest (0.4) recorded in the world before. Gastric cancer alone constitutes one-third of all cancers in Ardabil, the ASR of which is the highest reported from Iran up to now and one of the highest in the world. © 2003 Wiley-Liss, Inc.