We present the case of an 11 year-old Caucasian girl who presented chest pain of 12 weeks evolution, with no other symptoms and a negative physical examination. Lactate dehydrogenase levels were increased to 797 U/l, whereas beta-2-microglobulin (BM2) levels were normal. The thoracic CT showed a bulky mediastinal mass that occupied the pretracheal, paratracheal and right prevascular regions. The gallium scintigraphy showed high uptake in the mediastinic region; the bone scintigraphy was negative. Biopsy of the mediastinal mass revealed the presence of diffuse large B-cell non-Hodgkin's lymphoma. Treatment included 4 cycles of chemotherapy followed by 7 days of subcutaneous granulocyte colony-stimulating factor (G-CSF, Lenogastrim) at a dose of 5 mg/Kg/day. Following treatment, a CT scan was performed to evaluate response, finding a calcification of the mass without significant reduction of the overall size. Because CT was inconclusive in the assessment of response to therapy, a 18F-FDG PET scan was performed. The 18F-FDG PET scan did not show any pathological uptake in the mediastinum but revealed a splenic and bone marrow diffusely increased 18F-FDG uptake. The differential diagnosis included a secondary effect induced by G-CSF therapy as one of the main possibilities, but other possibilities such as a malignant infiltration by lymphoma could not be discarded. Therefore, a second 18F-FDG PET scan was performed 3 months later. This study showed no pathological findings, with a normal 18F-FDG uptake in the spleen and bone marrow. Thus, the benign and reactive nature of the splenic and bone marrow 18F-FDG increased uptake found in the previous study was confirmed. We consider that the stimulating effect that G-CSF therapy has on the spleen and bone marrow must be taken into account when performing a 18F-FDG PET scan, as it can be an important source of false-positive results.