PURPOSE The purposes of this study were: 1) to show bone marrow (BM) functional heterogeneity, 2) to demonstrate site-dependent responses of BM to cancer treatment utilizing whole body FDG-PET/CT and 3) to identify correlations between FDG uptake in different bone sites and long term complete blood count (CBC). METHODS Thirty two patients who had pre- and post-treatment FDG-PET/CT scans were selected retrospectively. Each patient received either head and neck radiation for cancer of the tongue, or pelvic radiation for rectal or cervical cancer with chemotherapy. Patients had FDG-PET/CT performed prior to the first radiation therapy session and at least one FDG-PET/CT after completion of the prescribed radiation therapy. RESULTS FDG uptake before radiotherapy was significantly different among bone regions (p < 0.01). This heterogeneity was felt to reflect site-dependent amounts of BM contents possibly due to structural and functional requirements. FDG uptake in the irradiated regions was significantly decreased on the first and second follow-ups after radiation. Feasibly, this could be due to a reduction in the number of active BM cells following intensive radiation in addition to concurrent chemotherapy. Overall, CBC significantly decreased after treatment. Correlation values of each hematological parameter with FDG uptake varied among skeletal regions and scan time points. FDG uptake in sacrum and lumbar regions had better correlation with white blood cells and neutrophils. CONCLUSIONS Longitudinal FDG-PET revealed a regional functional heterogeneity of the BM site-dependent response to treatment. Patients experienced immediate and prolonged marrow metabolic damage that correlates with hematological parameters. FDG-PET/CT may provide additional capabilities to assess BM health.