Objectives. To discuss the mutational features and their relationships with disease in a family with hereditary multiple osteochondroma (HMO) from Guangxi Province (GXBB‐1 family), China. Methods. Genomic DNA and total mRNA were extracted from peripheral blood cells of GXBB‐1 family members. Whole elements of the EXT1gene and its transcript, including exons, introns, exon‐intron boundaries, and coding sequence (CDS) clones, were amplified and sequenced. Allele‐specific PCR was used to confirm the position and type of mutation. Results. All patients from the GXBB‐1 family harbored the cosegregating heterozygous c.1056+1G>A mutation located in EXT1at an exon‐intron boundary. Another three single‐nucleotide polymorphisms (SNPs) were also detected in the patients, including IVS2+1G>A in intron 2, c.1844 T>C [p.Pro (CCT) 614Pro (CCC)] in exon 3, and c.2534G>A [p.Glu (GAG) 844Glu (GAA)] in exon 9. The latter two SNPs were synonymous variations. Conclusions. The heterozygous c.1056+1G>A mutation cosegregated with the phenotype, indicating that it is a pathogenic mutation in the GXBB‐1 family. This mutation is reported for the first time in Chinese HMO patients. IVS2+1G>A and c.2534G>A have no relationship with the occurrence of disease. However, c.1844 T>C and c.1056+1G>A are linked, and their interaction needs to be further studied. c.1844T>C is a new SNP that has not been reported internationally.