Key clinical message: a novel mutation in the SPTB gene (NM_001355436.2:intron12.1645-1G>A) was identified in a 22-year-old female with HS, highlighting the importance of genetic testing in confirming diagnoses of rare genetic disorders, expanding the mutation spectrum, and guiding personalized treatment in typical cases. This evidence concerns the gene SPTB and histiocytic sarcoma.