BACKGROUND: In 1980, Garland hypothesized that lower levels of vitamin D resulting from much weaker UV-B radiation at higher latitudes may account for the striking geographical pattern of cancer mortality. Further research has been conducted over the past 20 years. AIM: To perform a systematic review and meta-analysis of longitudinal studies on the association between serum 25 hydroxyvitamin D (25(OH)D) and the risk of colorectal cancer (CRC). METHODS: Relevant studies published until September 2008 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase of serum 25(OH)D by 20 ng/mL. Summary odds ratios (ORs) were calculated using meta-analysis methods. RESULTS: Overall, eight original articles reporting on the association between serum 25(OH) D and CRC risk were included. In meta-analyses, summary ORs (95% confidence intervals) for the incidence of CRC, colon cancer and rectal cancer associated with an increase of 25(OH)D by 20 ng/mL were 0.57 (0.43-0.76), 0.78 (0.54-1.13) and 0.41 (0.11-1.49). No indication for publication bias was found. CONCLUSIONS: Our results support suggestions that serum 25(OH)D is inversely related to CRC risk.