Regarding the H1N1pdm virus, it has been shown that prolonged virus shedding in cancer patients may occur, although such a phenomenon has only been documented through cases involving a single studied patient. Here, we prospectively and systematically collected information from a cohort of hospitalized cancer patients with severe H1N1pdm infections. These patients presented high mortality, prolonged viral shedding and H1N1pdm evolution without the emergence of oseltamivir resistance. This is the first study to address viral shedding and resistance in cancer patients with H1N1pdm infections; thus, it may provide insight into the role of cancer patients as potential human reservoirs for this pandemic virus. Unlike previous reports, our population was composed of hospitalized, severely immunocompromised cancer patients. Most of them were young, had hematologic malignancies and received chemotherapy and systemic steroids in the weeks that preceded the H1N1pdm infection. The patients were treated with oseltamivir in the early course of the infection. A total of 13 patients required intensive care and presented severe respiratory distress. In these patients, the mortality rates were higher than those observed for general ICU patients suffering from H1N1pdm infections as well as for non-critically ill cancer patients. Interestingly, during the influenza season, 14 patients with febrile neutropenia were identified as H1N1pdm cases, a condition that is not usually investigated in this scenario. However, febrile neutropenic cancer patients have an increased risk of developing respiratory distress and multi-organ failure. Therefore, screening for respiratory viruses and prompt initiation of oseltamivir treatment should be considered in these patients. Febrile neutropenia indicates a poor prognostic with respect to a patient’s outcome, but neutropenia duration in our cohort of patients was less than seven days. Thus, prolonged viral shedding might not have a correlation with neutropenia. We observed the persistence of H1N1pdm in 5 out of 10 patients studied for this purpose. In these individuals, viral shedding continued for at least 11 days, despite the use of oseltamivir. The median duration of viral shedding in our population was 23 days, and two pediatric patients with acute lymphoblastic leukemia showed even longer virus secretions, although it is TH-302 difficult to determine whether viral persistence was due to cancer per se or to acute lung injury and mechanical ventilation. Influenza shedding is not considered to last long, and it disappears seven days after the onset. Studies aimed at monitoring 2009 H1N1pdm virus shedding using randomized trials with appropriate controls, such as outpatients and hospitalized or immunocompromised.