Background: The purpose of this study was to determine the specific and detailed anatomic sites and morphologic characteristics of mediastinal lymph nodes on spiral computed tomography for the purpose of differentiation between sarcoidosis and Hodgkin's lymphoma. Material/Methods: Anatomical distribution of mediastinal lymph nodes on spiral CT was reviewed in 39 patients with sarcoidosis and 37 patients with Hodgkin's lymphoma using the International Association for the Study of Lung Cancer (IASLC) lymph node map. Other morphologic features such as lymph node calcification or coalescence of adjacent lymph nodes were also compared. Results: Zone 10 was involved more often in sarcoidosis than in Hodgkin's lymphoma. On the other hand, there was a higher tendency for presence of zone 1 and 3 as well as retrocrural and internal mammary lymphadenopathy in Hodgkin's lymphoma than in sarcoidosis. Sarcoidosis presented with intranodal calcifications more often than Hodgkin's lymphoma. Coalescence, pressure effect on adjacent structures and central cavitations were significantly more common in Hodgkin's lymphoma. Conclusions: Findings of the present study indicate that specific anatomical distribution and morphological patterns of mediastinal lymph nodes, as demonstrated on spiral CT, can be useful in differentiating sarcoidosis from Hodgkin's lymphoma.