OBJECTIVES To estimate total costs and assess primary cost drivers of treating newly diagnosed metastatic colorectal cancer (mCRC) after the introduction of biologic therapies. METHODS Using a large claims database of a US nationally commercially insured population, patients with newly diagnosed mCRC were identified from 2004 to 2006.  Patients were followed from initial mCRC diagnosis to either death, disenrollment, or December 31, 2006.   Using methods from published literature, the follow-up period for each patient was divided into three phases: diagnostic, treatment, and death. Average monthly costs for the three phases of disease were identified and asssigned as inpatient, outpatient, emergency room (ER), or medication-related costs (including chemotherapy and biologic agents).  RESULTS  A total of 2322 newly diagnosed mCRC patients were identified. Outpatient care was the cost driver during the diagnostic (42.6%) and treatment (51.7%) phases.  Inpatient care represented 39% of costs in the diagnostic phase largely due to surgical resection procedures (88.5%). Inpatient care was also the cost driver in the death phase (50.7%). Chemotherapies and biologics represented 15.6% and 16.2% of costs in the treatment phase; and 12.1% and 11.7% of total costs across all phases of disease, respectively.   CONCLUSIONS  Inpatient and outpatient care were the key cost drivers in the medical management of mCRC.  Biologics represented 16.2% of treatment phase costs and 11.7% of all costs incurred by mCRC patients across all phases of disease.