Greater trochanteric pain syndrome (GTPS) is a pathology that can involve the trochanteric bursa or the tendons which attach to the greater trochanter. To clarify the potential importance of bursa versus tendon pathology and of substance P (SP) in contributing to pain in this condition tendon and bursa tissue biopsies were obtained from 34 patients with GTPS and 29 control subjects. Specimens were evaluated via light microscopy for histopathological and morphological differences, as well as using immunohistochemistry for macrophages (CD68), inflammatory cells (CD45) and SP. Bursa [stroma score, mean (SD): 4.18 (1.65) vs. 2.53 (1.61), p = 0.051] and tendon [Bonar score, mean (SD): GTPS mean (SD) 12.65 (2.0), control (10.43 (4.84), p = 0.04] from subjects with GTPS demonstrated more extensive signs of pathology than specimens from control subjects. There was a significantly greater presence of SP in the bursa (frequency: 9/12 vs. 6/16, p = 0.047), but not in the tendon (8/12 vs. 8/15, p = 0.484) of subjects with GTPS compared to controls. An increased presence of SP in the trochanteric bursa may be related to the pain associated with GTPS.