Carpal tunnel syndrome (CTS) is a common entrapment neuropathy in which one of the body’s peripheral nerves becomes pinched or crushed. Transforming growth factor beta 1 (TGF-β1) plays an important role in the pathogenesis of CTS. An association between TGF-β1 polymorphisms and the susceptibility or progression of a number of diseases has been reported. In this study, three TGF-β1 single nucleotide polymorphisms (SNPs), serum TGF-β1, and macrophage inflammatory protein 1 beta (MIP-1β) were investigated as potential diagnostic markers for the progression of CTS in Egyptian patients. One hundred CTS patients and 100 healthy controls were recruited for the study. TGF-β1 SNPs +915G/C, −509C/T and −800G/A were determined by TaqMan genotyping assay. Serum TGF-β1 and MIP-1β levels were measured by ELISA. Serum TGF-β1 and MIP-1β levels increased significantly and were strongly correlated with the occurrence of CTS. The C allele of +915G/C, the T allele of −509C/T, and the G allele of −800G/A occurred more frequently in patients from CTS than in controls. The serum levels of TGF-β1 and MIP-1β in the group of carriers of the genotypes +915G/C GC and CC, the genotype −509C/T TT and the genotype −800G/A GA and AA were significantly higher in CTS patients. TGF-β1 and its +915G/C, −509C/T, and −800G/A SNPs and MIP-1β could be useful prognostic markers for the occurrence of CTS.