The prevalence, severity and symptom profiles for major depressive disorder (MDD) were compared in samples of boys and adolescents with and without an autism spectrum disorder (ASD). Self-reports were obtained on the Depression subscale of the Child and Adolescent Symptoms Inventory (CASI-D) with 70 ASD and 50 non-ASD male participants between the ages of 8 and 18 from Queensland, Australia who were matched for age and IQ. Results indicated that the ASD participants had significantly higher total CASI-D scores, a greater proportion of participants who qualified for a diagnosis of MDD, and over 50% higher scores for 8 of the 10 CASI-D symptoms than non-ASD participants. The MDD profiles for the ASD participants were dominated by anhedonia. Issues for assessment and diagnosis of comorbid MDD in young males with an ASD, plus targeted treatment planning that directly addresses their MDD profile, are discussed.