A 61-year-old man presented with spontaneous pneumothorax. After diagnosis of emphysemic bullae, the patient underwent talc pleurodesis and had no further complaints. Five years later a routine chest X-ray showed suspicious pleural lesions in addition to the emphysema, which was deemed compatible with the known history of talc pleurodesis. Subsequent chest CT, however, revealed one lesion in the right lung that appeared not typical for this condition in addition to multiple lesions in pleural proximity. FDG-PET/CT demonstrated high glucose uptake in all the lesions. Subsequent needle biopsy of the suspicious intrapulmonary and also of one mediastinal lesion yielded the histopathological diagnosis of talcum granuloma with long-standing calculous fibrotic changes and no evidence of malignancy. This report on PET/CT after talc pleurodesis addresses the potential pitfalls caused by this condition, as chronic granulomatous reactions, like other inflammatory lesions, may account for highly increased FDG uptake which should be interpreted with caution and not simply read as a sign of malignancy. PET/CT offers the opportunity to exactly localize the areas of increased FDG uptake within regions of pleural thickening caused by talc deposition, however, the dilemma of misleading FDG accumulation cannot be solved by this hybrid imaging modality.