Neutropenic enteritis (NE) or enterocolitis (NEC) is a rare, but potentially life-threatening side effect of neutropenia-inducing chemotherapy agents. Generally, its occurrence is attributed to leukemiaassociated chemotherapies. Two cases of NE have been reported after the appliance of pemetrexed for treatment of non-small cell lung cancers. To our knowledge, NE has never been reported due to treatment with pemetrexed for malignant pleural mesothelioma (MPM). We present a case of MPM in a 77-year-old male suffering from severe NE one week after the seventeenth cycle of pemetrexed in the course of maintenance therapy for MPM, which could be treated successfully with antibiotic coverage and supportive measures. Concomitantly the patient showed a severe hyperpigmentation of his entire integument sparing the palms of both hands and the soles of his feet. After exclusion of alternative causes of skin hyperpigmentation, a pemetrexed-induced cutaneous hyperpigmentation was assumed according to two previous case reports. A combination of both pemetrexed-induced side effects in one patient has not been reported to date.