The role of radial-endobronchial ultrasound (R-EBUS) assisted transbronchial biopsy (TBB) for the diagnosis of peripheral pulmonary lesions is well established. However, no study has addressed its safety and value in hemato-oncological patients presenting with non-resolving infiltrates during persistent febrile neutropenia. To assess safety and feasibility of R-EBUS assisted TBB in severe thrombocytopenic and neutropenic patients. Over a period of 18 months, eight patients were assessed with R-EBUS assisted TBB after adequate platelet transfusion. This technique allowed precise localisation and sampling of the pulmonary lesions in seven of eight patients. In the seven patients, R-EBUS assisted TBB enabled treatment optimization. Invasive fungal infection was diagnosed in four patients, idiopathic acute fibrinous and organising pneumonia in three patients, and a granulomatous inflammation of undetermined origin in one patient. Importantly, no complications, such as bleeding, were observed. R-EBUS assisted TBB is a promising and safe procedure for the evaluation of nonresolving pulmonary infiltrates in febrile neutropenic hemato-oncological patients.