Background: The aim of the present study is to investigate the effects produced by a treatment with myo-Inositol (myo-Ins) in women presenting polycystic ovary syndrome (PCOS) of different phenotypes. Methods: We performed a retrospective study to evaluate whether patients presenting different PCOS phenotypes, treated for 6 months with myo-Ins, might exhibit a differential response to the treatment. On this premise, we clustered women with PCOS phenotypes A, B, and C in the first study group (hyperandrogenic PCOS or H-PCOS), and women presenting PCOS phenotype D in a separate study group (non-hyperandrogenic PCOS or NH-PCOS) to evaluate if the presence of hyperandrogenism, shared by H-PCOS, might imply a metabolic/endocrine condition rather than a gynecological issue. Results: The administration of myo-Ins induced a significant improvement in metabolic and endocrine parameters in H-PCOS, while the effects on NH-PCOS were negligible. Additionally, myo-Ins treatment improved the endometrial thickness of H-PCOS. Conclusions: Subjects selected for the study exhibited a differential response to myo-Ins therapy according to their PCOS phenotypes. The data suggest that the same treatment might not equally improve the parameters of the PCOS condition in each sub-group of patients. It is crucial to distinguish the various phenotypes to properly select the therapeutical approach.