Central studies carried out on vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) excluded patients receiving immunosuppressive therapy and those diagnosed with an immunosuppressive condition. Moreover, there are no data on vaccine efficacy regarding older patients with cancer. The primary objective was to evaluate the seroprevalence of the SARS-CoV2 IgG in older patients (aged ≥80 years) diagnosed with solid or hematol. malignancies, one month after administering the second dose of the BNT162b2 vaccine. We screened 74 older patients with cancer, 45 of them accepted to receive the vaccination and collected serum samples from 36 patients; a group of medical doctors and nurses from our hospital was used as a control in a 1:2 ratio. The median age was 82 years (range 80-89). Median serum IgG were 2396,10 AU/mL (range 0-32,763,00) in patients with cancer and 8737,49 AU/mL (398.90-976,280,00) in the control group, p < 0.0001. Addnl. subgroup analyses were performed comparing males and females, patients treated with chemotherapy vs. other therapies (immunotherapy, targeted therapy), solid tumors vs. hematol. malignancies, early (I-II) vs. advanced (III-IV) stage of disease, continuative corticosteroid use or not. None of them reached statistical significance. Our study shows for the first time that patients with cancer aged ≥80 years can have a serol. response to the BNT162b2 COVID-19 vaccine one month after vaccination and consequently support the vaccination campaign currently underway in this frail population.