Objective: We aimed to identify a rapid, accurate, and accessible biomarker in the early stages of COVID-19 that can determine the prognosis of the disease in cancer patients. Methods: A total number of 241 patients with solid cancers who had a COVID-19 diagnosis between March 2020 and February 2022 were included in the study. Factors and ten different markers of inflammation were analyzed by year of diagnosis of COVID-19 and grouped by severity of infection. Results: Hospitalization, referral to the intensive care unit (ICU), mechanical ventilation, and death were more frequent in 2020 than in 2021 and 2022 (mortality rates, respectively, were 18.8%, 3.8%, and 2.5%). Bilateral lung involvement and chronic lung disease were independent risk factors for severe disease in 2020. In 2021–2022, only bilateral lung involvement was found as an independent risk factor for severe disease. The neutrophil-to-lymphocyte platelet ratio (NLPR) with the highest area under the curve (AUC) value in 2020 had a sensitivity of 71.4% and specificity of 73.3% in detecting severe disease (cut-off > 0.0241, Area Under the Curve (AUC) = 0.842, p <.001). In 2021–2022, the sensitivity of the C-reactive protein-to-lymphocyte ratio (CRP/L) with the highest AUC value was 70.0%, and the specificity was 73.3% (cut-off > 36.7, AUC = 0.829, p =.001). Conclusions: This is the first study to investigate the distribution and characteristics of cancer patients, with a focus on the years of their COVID-19 diagnosis. Based on the data from our study, bilateral lung involvement is an independent factor for severe disease, and the CRP/L inflammation index appears to be the most reliable prognostic marker.