Objectives: The Center for Epidemiologic Studies Depression Scale (CES-D) was specifically created to assess depression in cancer patients. However, to date, the CES-D has not been validated in Farsi. Therefore, this study aimed to assess the psychometric properties of the CES-D in Iranian cancer patients. Methods: During a three-month period (October to December, 2015), a total of 380 cancer patients completed a Farsi version of the CES-D. The construct validity of the scale was evaluated by exploratory factor analysis. Reliability was assessed using Cronbach’s alpha and McDonald Omega. All of the statistical procedure were run by SPSS 22 (SPSS Inc., Chicago, IL, USA). Results: The construct validity of the CES-D determined three factors (somatic affect, negative affect, and positive affect), which explained 65.60% of the total variance. The internal consistency was greater than 0.70. Conclusion: Findings revealed that the Farsi version of the CES-D has acceptable validity and reliability, which can be used to measure depression in Iranian cancer patients.