Calcium (Ca(2+))-containing crystals (CCs), including basic Ca(2+) phosphate (BCP) and Ca(2+) pyrophosphate dihydrate (CPPD) crystals, are associated with severe forms of osteoarthritis (OA). Growing evidence supports a role for abnormal articular cartilage mineralization in the pathogenesis of OA. However, the role of Ca(2+) compounds in this mineralization process remains poorly understood. Six patients, who underwent total knee joint replacement for primary OA, have been considered in this study. Cartilage from femoral condyles and tibial plateaus in the medial and lateral compartments was collected as 1 mm-thick slices cut tangentially to the articular surface. First, CCs presence and biochemical composition were assessed using Fourier transform infrared spectroscopy (FT-IR). Next, Ca(2+) compound biochemical form was further assessed using X-ray absorption spectroscopy (XAS) performed at the Ca(2+) K-absorption edge. Overall, 12 cartilage samples were assessed. Using FT-IR, BCP and CPPD crystals were detected in four and three out of 12 samples, respectively. Ca(2+) compound biochemical forms differed between areas with versus without CCs, when compared using XAS. The complete set of data shows that XANES spectroscopy can be used to accurately characterize sparse CCs in human OA cartilage. It is found that Ca(2+) compounds differ between calcified and non-calcified cartilage areas. In calcified areas they appear to be mainly involved in calcifications, namely Ca(2+) crystals.