Background: Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose: To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods: Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results: The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.220.03 x 10(-3)mm(2)/s) was significantly (P<0.001) lower than that of non-cartilaginous tumor cell necrosis without stroma disintegration (25/91, ADC = 1.77 +/- 0.03 x 10(-3) mm(2)/s), cartilaginous viable tumor (14/91, ADC = 2.19 +/- 0.04 x 10(-3) mm(2)/s), and cystic areas including liquefied necrosis, blood space, and secondary aneurysmal bone cyst (14/91, ADC = 2.29 +/- 0.05 x 10(-3) mm(2)/s). The mean ADC value of non-cartilaginous tumor cell necrosis was also significantly (P<0.001) smaller than those of viable cartilaginous tumor and cystic/hemorrhagic necrosis whereas the mean ADC values were not significantly (P>0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion: DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.