Surface defects have a central position in diagnosis of articular pathology. Recognizing the limitations of standard radiologic techniques and those imposed by positioning and averaging artifacts on CT evaluation, direct visualization of surface defects was pursued to identify disease characteristics that would facilitate interpretation of radiologic findings. Epi-illumination surface microscopy was utilized to examine macroscopically recognized articular surface defects in individuals in the Hamann-Todd, Terry, and Huntington human skeletal collections with previously verified diagnoses of rheumatoid arthritis, spondyloarthropathy, juvenile inflammatory arthritis (JIA), calcium pyrophosphate deposition disease (CPPD), gout, metastatic cancer, multiple myeloma, septic arthritis, tuberculosis, fungal arthritis, histiocytosis and sickle cell anemia (Rothschild and Rothschild Clin Infect Dis 20(5):1402-1408, 1995; Rothschild et al. Amer J Phys Anthropol 82(4):441-449, 1990; Rothschild and Rothschild Amer J Phys Anthropol 96(4):357-563, 1995; Rothschild and Woods Clin Exp Rheumatol 10(2):117-122, 1992; Barrett and Keat Radiographics 24(6):1679-1691, 2004; Rothschild and Heathcote Amer J Phys Anthropol 98(4):519-525, 1995; Rothschild and Woods Am J Phys Anthropol 85:25-34, 1991; Hershkovitz et al. Amer J Phys Anthropol 106(1):47-60, 1998; Winland et al. Amer J Phys Anthropol 24:S243, 1997; Rothschild et al. Clin Exp Rheumatol 10(6):557-564, 1992; Rothschild and Martin , 2006; Rothschild et al. Amer J Phys Anthropol 102(2):249-264, 1997). Observed alterations were compared with standard radiographs. Fronts of resorption distinguished inflammatory arthritis from those caused by the other disorders studied. Multiple myeloma, fungal disease, and gout are expansile character; the latter accompanied by reactive new bone formation more prominent than that noted with spondyloarthropathy and JIA. Those were clearly distinguished from the crumbling alterations found with CPPD. Histiocytosis had a unique crenulated appearance, while nodules were prominent with syphilis. Defects in sickle cell anemia had ivory fragments at their base. These findings provided explanation for radiologic observations. Direct surface microscopy revealed characteristics apparently pathognomonic for specific disorders and facilitated distinguishing among them. The technique provides visualization an order of magnitude greater than that available with clinical radiologic techniques and identifies new characteristics which should facilitate clinical diagnoses. This demonstrates that there would be value to the development of higher resolution, clinically applicable imaging techniques.