Background: Cancer is as a predictor of adverse outcomes in symptomatic pulmonary embolism (PE). Nowadays, the increasing diagnosis of incidental thrombosis in scheduled CT scans implies a change in PE presentation. Clinical guidelines suggest that home treatment is an appropriate alternative for selected low-risk PE-patients although specific data regarding this approach in cancer population remain scarce. The aim of the present report is to describe clinical characteristics, outcomes and feasibility of outpatient management of patients with cancer-related PEs. Methods: EPIPHANY is an ongoing multicenter observational study of consecutive cancer-related PEs (acute symptomatic and incidentally-found in scheduled CT scans) recruited from daily clinical practice with a minimum 3-month follow-up after PE. Outpatient management was considered on discharge from hospital less than 24 hours after PE diagnosis. Results: From January 2006 to September 2013 we enrolled 562 cancer patients with PE, 385 of whom (68%) were treated in hospital and 177 (32%) were managed as outpatients. Most patients treated at home (93%) had advanced cancer (TNM stages III-IV), most (77%) were being treated with chemotherapy or biological/targeted therapies and 6% underwent major surgery within 1 month. Patients treated at home more likely had an incidentally-detected PE (91% vs. 35%; p<0.001) and were ‘truly asymptomatic’ cases (86% vs. 30.5%; p<0.001) compared to patients treated with conventional hospitalization. The rate of major complications within 15 days of PE in patients treated at home was 3.4% (95% CI, 1.9-4.9%). Overall mortality rates were lower in outpatients at 30 days (2.3% vs. 21%; p<0.001) and 90 days (9.6% vs. 33%; p<0.001) of follow-up compared to patients treated in hospital. The most frequent cause of death was cancer progression in both groups. The rates of venous thromboembolic recurrences and major bleeding events at 30 and 90 days were comparable in both groups. Conclusions: Cancer-related PE can be managed at home in a high proportion of patients, especially those incidentally diagnosed. Further studies addressed to better define low risk patients in this setting should be developed.