Northern Iran counts as one of the highest prevalence regions for esophageal cancer (EC) worldwide. This study was designed to assess the epidemiologic aspects of EC in north central and northwest Iran over a 10 year period. The Guilan cancer registry study (GCRS) is a population- based cancer registry study featuring retrospective (1996-2003) and prospective (2004-2005) phases. A detailed questionnaire based on WHO standards for cancer registratration was applied to gather the required information. Two trained physicians coded information using ICD-O-3 in close coordination with an expert pathologist. A total of 19,936 cases of malignancy (mean age 55.4±18.0 years, range: 1-98 years) were registered, including 1,147 cases (670 males, 447 female; mean age: 64.0±11.5 years) of EC. In 1996 the male/female ratio among patients with EC was 1.25 which increased to 1.53 in 2005. The lower third of the esophagus still remained the most common site of tumors. The average age-standardized rate (ASR) was 6.9 and 4.1 per 105 men and women, respectively. In 1996, the ASRs were 7.2 and 5.2 per 105 men and women which decreased to 6.9 and 4.1 per 105 in 2004-2005. Squamous cell carcinoma (SCC) was the most prevalent histological subtype of EC accounting over 80% of cases. However the prevalence of adenocarcinoma (ADC) showed an increase to 18.4%. Guilan province may be considered a relatively low incidence region for EC.