This study evaluates the pathogenetic role of the perineural connective tissue and foot fasciae in Civinini-Morton's neuroma. Eleven feet (seven male, four female; mean age: 70.9 years) were dissected to analyse the anatomy of inter-metatarsal space, particularly the dorsal and plantar fasciae and metatarsal transverse ligament (DMTL). The macrosections were prepared for microscopic analysis. Ten Civinini-Morton neuromas obtained from surgery were also analysed. Magnetic resonance images (MRIs) from 40 patients and 29 controls were compared. Dissections showed that the width of the inter-metatarsal space is established by two fibrous structures: the dorsal foot fascia and the DMTL, which, together, connect the metatarsal bones and resist their splaying. Interosseous muscles spread out into the dorsal fascia of the foot, defining its basal tension. The common digital plantar nerve (CDPN) is encased in concentric layers of fibrous and loose connective tissue, continuous with the vascular sheath and deep foot fascia. Outside this sheath, fibroelastic septa, from DMTL to plantar fascia, and little fat lobules are present, further protecting the nerve against compressive stress. The MRI study revealed high inter-individual variability in the forefoot structures, although only the thickness of the dorsal fascia represented a statistically significant difference between cases and controls. It was hypothesized that alterations in foot support and altered biomechanics act on the interosseous muscles, increasing the stiffness of the dorsal fascia, particularly at the points where these muscles are inserted. Chronic rigidity of this fascia increases the stiffness of the inter-metatarsal space, leading to entrapment of the CDPN.