Background: Palm and sole skin eruptions have a broad differential diagnosis. It is particularly important to recognize common causes as well as their association with certain chemotherapy regimens such as Capecitabine. Case report: A 79-year-old woman presented with a painful rash on her hands and feet for 1 week. She had metastatic colon cancer and was in her third week of treatment with capecitabine. Her diagnosis was a medication side-effect from chemotherapy. Capecitabine was stopped and she had some clinical improvement over the next two days. She was discharged with oncology follow up for resumption of Capecitabine at a lower dose with improvement in her rash 3 weeks later. Discussion: Skin rashes are a commonly encountered complaint in patients in the inpatient and outpatient setting. It is important to maintain a broad differential diagnosis in those with rashes of the palmoplantar surfaces of the hands and feet. Recognizing skin changes as a possible manifestation of underlying malignancy or a medication side-effect is key in appropriate diagnosis and treatment.