The purpose of this study was to evaluate a culturally adapted cognitive-behavioral treatment (CBT) for major depression among Hispanics in primary care. Cultural adaptations were applied based on a range of cultural considerations described in the literature. Fifteen Hispanic primary care patients with major depression were enrolled. All participants received the 12-session intervention and completed baseline, posttreatment, and 6-month follow-up assessments. Four participants (27%) dropped out of the treatment. Analyses focused on changes from baseline functioning using a Wilcoxon Signed Rank Test. Results showed significant reductions in depressive, anxious, and somatic symptoms at posttreatment and 6-month follow-up. Mean reduction of depressive symptoms at posttreatment was 57%. Findings of acceptable treatment retention rates and clinically meaningful reductions in depressive symptoms showed promise for this intervention to treat Hispanics with major depression. Future studies should conduct a more rigorously controlled evaluation of this intervention.