BACKGROUND: Patients seeking second opinions are a challenge for the colorectal cancer provider because of complexity, failed therapeutic relationship with another provider, need for reassurance, and desire for exploration of treatment options. OBJECTIVE: The purpose of this study was to describe the patient and treatment characteristics of patients seeking initial and second opinions in colorectal cancer care at a multidisciplinary colorectal cancer clinic. DESIGN: This was a retrospective cohort study. SETTINGS: A prospectively collected clinical registry of a multidisciplinary colorectal cancer clinic was included. PATIENTS: The study included patients with colon or rectal cancer seen from 2012 to 2017. MAIN OUTCOME MEASURES: Data were analyzed for initial versus second opinion and demographic and clinical characteristics. RESULTS: Of 1711 patients with colorectal cancer, 1008 (58.9%) sought an initial opinion and 700 (40.9%) sought a second opinion. As compared with initial-opinion patients, second-opinion patients were more likely to have stage IV disease (OR = 1.94 (95% CI, 1.47-2.58)), recurrent disease (OR = 1.67 (95% CI, 1.13-2.46)), and be ages 40 to 49 years (OR = 1.47 (95% CI, 1.02-2.12)). Initial- and second-opinion cohorts were similar in terms of sex, race, and proportion of colon versus rectal cancer. Among second-opinion patients, 246 (35%) transitioned their care to the multidisciplinary colorectal cancer clinic. LIMITATIONS: We were unable to capture the final treatment plan for those patients who did not transfer care to the multidisciplinary colorectal cancer clinic. CONCLUSIONS: Patients seeking a second opinion represent a unique subset of patients with colorectal cancer. In general, they are younger and more likely to have stage IV or recurrent disease than patients seeking an initial opinion. Although transfer of care to a multidisciplinary colorectal cancer clinic after second opinion is lower than for initial consultations, multidisciplinary colorectal cancer clinics provide an important role for patients with complex disease characteristics and treatment needs. See Video Abstract at http://links.lww.com/DCR/B192.