Background: Since the beginning of SARS-CoV-2 pandemic, it has been widely recognized that children and adolescents seem to have milder clinical courses as compared to adult counterparts. However, there is concern that vulnerable collectives including pediatric patients treated for cancer or under immunosuppression may be at higher risk. Methods: We retrospectively collected Spanish COVID-19 cases in children and adolescents with solid and hematological malignancies, non-malignant chronic hematologic conditions, and post allogeneic-stem cell transplantation, from the beginning of the pandemic on January 31 to April 24, 2020. Results: We included 47 cases with RT-PCR positive COVID-19 from 41 centers in Spain, where 97.6% of pediatric patients are treated for cancer. In most cases (76.6%), infection was asymptomatic, or symptoms were mild. Severe illness was observed in 14.9% of cases with respiratory distress and/or hypoxemia, and 8.5% required admission to the PICU. Symptomatic patients received supportive care associated with antiviral and immunomodulatory agents depending upon severity. Anticancer therapy was withhold in the majority of cases during the infection course. Most patients recovered from COVID-19. Two deaths were reported. Conclusion: In our cohort, most children receiving anticancer chemotherapy presented a mild clinical course and had a good outcome. Highly immunosuppressed patients with major comorbidities were at higher risk of severe infections. Among this fragile collective, individualized expert discussion is critical for anti-infectious therapy and appropriate anticancer treatment.