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Background: Imatinib mesylate (IM) is the standard treatment for BCR-ABL-positive chronic myelogenous leukemia (CML) and is the first-line adjuvant and palliative treatment for metastatic and inoperable gastrointestinal stromal tumor (GIST). IM is not known to be associated with an increased risk for development of granulomatous diseases., Methods: We describe our experience with 2 patients (42 and 62 years of age) who developed granulomatous disease during IM treatment for metastatic GIST., Results: Mean duration of IM treatment was 12 (range 8-16) months. Enlarged lymph nodes with increased metabolism on FDG-PET-CT examination were detected and resected. Affected sites were supraclavicular (1) and subcarinal/mediastinal (1) lymph nodes. Histological examination revealed caseating and non-caseating granulomas suggestive of tuberculosis and sarcoidosis, respectively. Mycobacterium tuberculosis was detected by PCR in lymph nodes of 1 patient who was then successfully treated by anti-tuberculous agents. The other patient had negative sputum test for acid-fast bacilli and PCR-DNA-analysis was negative for M. tuberculosis and other mycobacteria. He received no anti-tuberculous therapy and had no evidence of progressive lymphadenopathy or new lung lesions during follow-up., Conclusion: Our observations underline the necessity to obtain biopsy material from enlarged or metabolically active lymph nodes developing during IM treatment for timely diagnosis and appropriate treatment of these rare complications. Follow-up without treatment is safe for patients without detectable microorganisms by sputum examination and PCR.