Unprecedented immunization campaigns have been rolled out worldwide in an attempt to contain the ongoing COVID-19 pandemic. Multiple vaccines were brought to the market, among two utilizing novel messenger ribonucleic acid technology. Despite their undisputed success in decreasing COVID-19-associated hospitalizations and mortality, various adverse events have been reported. The emergence of malignant lymphoma is one of such rare adverse events that has raised concern, although an understanding of the mechanisms potentially involved remains lacking. Herein, we present the first case of B-cell lymphoblastic lymphoma following intravenous high-dose mRNA COVID-19 vaccination (BNT162b2) in a BALB/c mouse. Two days following booster vaccination (i.e., 16 days after prime), at only 14 weeks of age, our animal suffered spontaneous death with marked organomegaly and diffuse malignant infiltration of multiple extranodal organs (heart, lung, liver, kidney, spleen) by lymphoid neoplasm. Immunohistochemical examination revealed organ sections positive for CD19, terminal deoxynucleotidyl transferase, and c-MYC, compatible with a B-cell lymphoblastic lymphoma immunophenotype. Our murine case adds to previous clinical reports on malignant lymphoma development following novel mRNA COVID-19 vaccination, although a demonstration of direct causality remains difficult. Extra vigilance is required, with conscientious reporting of similar cases and a further investigation of the mechanisms of action explaining the aforementioned association.