CONTEXT: Diabetes mellitus appears to be a risk factor for some cancers, but the effect of preexisting diabetes on all-cause mortality in newly diagnosed cancer patients is less clear. OBJECTIVE: To perform a systematic review and meta-analysis comparing overall survival in cancer patients with and without preexisting diabetes. DATA SOURCES: We searched MEDLINE and EMBASE through May 15, 2008, including references of qualifying articles. STUDY SELECTION: English-language, original investigations in humans with at least 3 months of follow-up were included. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Of 7858 titles identified in our original search, 48 articles met our criteria. DATA EXTRACTION: One reviewer performed a full abstraction and other reviewers verified accuracy. We contacted authors and obtained additional information for 3 articles with insufficient reported data. RESULTS: Studies reporting cumulative survival rates were summarized qualitatively. Studies reporting Cox proportional hazard ratios (HRs) or Poisson relative risks were combined in a meta-analysis. A random-effects model meta-analysis of 23 articles showed that diabetes was associated with an increased mortality HR of 1.41 (95% confidence interval [CI], 1.28-1.55) compared with normoglycemic individuals across all cancer types. Subgroup analyses by type of cancer showed increased risk for cancers of the endometrium (HR, 1.76; 95% CI, 1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95% CI, 1.24-1.41). CONCLUSIONS: Patients diagnosed with cancer who have preexisting diabetes are at increased risk for long-term, all-cause mortality compared with those without diabetes.