We report on epidemiology, features, outcome, and domiciliary management of pain in patients with advanced hematological malignancies followed by an experienced hospital-based home care (HC) team. Out of 469 patients, 244 (52%) experienced a total of 284 pain syndromes. Pain intensity was rated from mild to moderate in 31% and from moderate to severe in 69% of them. The diagnosed pain mechanisms were deep somatic in 56%, superficial somatic in 15%, visceral 14%, mixed 8%, and neuropathic in 7% of pain syndromes, respectively. Incident pain was observed in 38% of all pain syndromes. In every diagnostic group, deep somatic pain was prevalent. Moreover, 85% of visceral pain syndromes were observed in patients affected by non-Hodgkin's lymphoma (NHL). In addition, out of 284 pain syndromes, 150 (51%) were caused by bone involvement. The most frequent recognized pain provocative mechanisms were bone marrow expansions, osteolysis, lymph node enlargement, and mucositis. In our experience, an approach based on the association of causal therapies and analgesics allows optimal control of most pain syndromes. Therefore, pain is a major problem in patients affected by advanced hematological malignancies, and its management can be effective and feasible when carried out by a skilled HC team.