We report a case of cholestatic jaundice and pseudomembranous colitis (PMC) following combination therapy with docetaxel and doxorubicin. This clinical syndrome has not been previously reported with this combination. In particular, this is the first report of non-Clostridium difficile-associated PMC with docetaxel-based chemotherapy. Docetaxel is principally metabolized by the hepatic cytochrome P450 mixed-function oxidases, in particular by the isoform CYP3A. This patient was on long-term erythromycin prophylaxis following splenectomy. Erythromycin is a known inhibitor of CYP3A. We postulate that erythromycin probably contributed to the observed clinical syndrome. Clinicians should be aware of potential drug interactions, when unusual toxicities occur with novel combinations of chemotherapeutic agents.