BACKGROUND Large health care databases are increasingly used to examine the dissemination and benefits and harms of chemotherapy treatment in routine practice, particularly among patients excluded from trials (eg, the elderly). Misclassification of chemotherapy could bias estimates of frequency and association, warranting an updated assessment. METHODS We evaluated the validity of Medicare claims to identify receipt of chemotherapy and specific agents delivered to elderly stage II/III colorectal (CRC), in situ/early-stage breast, non-small-cell lung, and ovarian cancer patients using the National Cancer Institute's Patterns of Care studies (POC) as the gold standard. The POC collected data on chemotherapy treatment by reabstracting hospital records, contacting physicians, and reviewing medical records. Patients' POC data were linked and compared with their Medicare claims for 2 to 12 months postdiagnosis. κ, sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated for the receipt of any chemotherapy and specific agents. RESULTS Sensitivity and specificity of Medicare claims to identify any chemotherapy were high across all cancer sites. We found substantial variation in validity across agents, by site and administration modality. Capecitabine, an oral CRC treatment, was identified in claims with high specificity (98%) but low sensitivity (47%), whereas oxaliplatin, an intravenously administered CRC agent had higher sensitivity (75%) and similar specificity (97%). CONCLUSIONS Receipt of chemotherapy and specific intravenous agents can be identified using Medicare claims, showing improvement from prior reports; yet, variation exists. Future studies should assess newly approved agents and the impact of coverage decisions for these agents under the Medicare Part D program.