Hepatic and peritoneal metastases are the most frequent metastatic lesions in patients with gastrointestinal stromal tumors (GIST), and may result in intra- or extrahepatic cholestasis and altered drug metabolism. While the tyrosine kinase inhibitor imatinib, which has been recently shown to represent the treatment of choice for GIST, is primarily metabolized by the liver, data on the pharmacokinetics and the tolerability of imatinib in patients with increased cholestasis parameters are not yet available. We here report on two patients who received imatinib in the presence of increased bilirubin and/or cholestasis parameters. With a follow-up duration of 3–4 months, we observed no toxicities outside of well-known side effects including some degree of myelosuppression and fluid retention. This report may aid in the decision of imatinib being given under close surveillance to this kind of patients.