The present case study investigated a rare case of quadruple squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation (HSCT) for leukemia. The main aim of the case study was to determine the pathogenesis and provide novel methods for the diagnosis and treatment of similar cases. The presence of genetic mutations in the p53, EGFR, KRAS and BRAF genes were analyzed and the presence of microsatellite instability (MSI) was determined. In addition, the expression levels of the proteins p53 and EGFR were investigated. The results identified a genetic mutation in p53, of which its expression levels were upregulated. In addition, the majority of the tumor tissues presented with MSI. Therefore, the present findings suggested that the genetic mutations in p53 caused by MSI following allogeneic HSCT may promote tumorigenesis. In addition, the expression levels of the EGFR protein were upregulated, leading to an increase in MAPK signaling pathway activation, which may also serve an important role.Keywords: graft-versus-host disease; hematopoietic cell transplantation; immune state; multiple primary carcinomas; p53.