PURPOSE: Contrast-enhanced digital mammography (CEDM) is an advanced breast imaging technique using iodinated intravenous contrast to detect breast cancer. This article describes imaging features of a skin contamination artifact on CEDM that mimics in-situ carcinoma in a case series. MATERIALS AND METHODS: Five patients were identified whose CEDM images demonstrated apparent calcifications and non-mass enhancement suspicious for in-situ carcinoma, with no subsequent evidence of disease. Retrospective image analysis was performed on the unprocessed image data, processed images, and imaging parameters. Dual-energy mammographic technique was performed on two breast phantoms with varying degrees of topical contrast contamination. RESULTS: Temporal analysis confirmed the suspicious finding was neither an abnormality of the compression paddle nor the receptor. Comparison of LE and HE images demonstrated the suspicious finding attenuated near the K-edge of iodine, suggesting contrast contamination. Iodinated contrast applied to the surface of breast phantoms replicated the artifact, with a pattern of apparent enhancement similar to the appearance of in-situ carcinoma. CONCLUSION: Skin contamination with iodinated contrast can result in an artifact on post-contrast digital mammography that mimics the appearance of in-situ carcinoma.