Eighty-eight Staphylococcus aureus clinical isolates meeting criteria for borderline oxacillin resistance (intermediate susceptibility or resistance to oxacillin but susceptibility to amoxicillin/clavulanic acid upon disk diffusion testing) were studied to determine optimal test techniques and conditions for differentiating borderline oxacillin-resistant Staphylococcus aureus (BORSA) from methicillin-resistant Staphylococcus aureus (MRSA). Further testing revealed three distinct resistance patterns: 61 strains (69%) consistently met BORSA criteria and had average beta-lactamase levels five- to six-fold higher than oxacillin-susceptible controls; 11 strains (13%) were markedly heteroresistant MRSA with delayed appearance of resistant colonies leading to spurious susceptibility to amoxicillin/clavulanic acid; 16 strains (18%) appeared to be oxacillin-susceptible on repetitive testing. Under conditions used to elicit intrinsic methicillin resistance in Staphylococcus aureus, a large percentage of BORSA appeared resistant to amoxicillin/clavulanic acid. This clearly shows that BORSA may be misidentified as MRSA while heteroresistant MRSA may appear to be BORSA. It is concluded that amoxicillin/clavulanic acid zone sizes should be measured after a full 24 hours of incubation, that susceptibility testing of Staphylococcus aureus under certain environmental conditions should be interpreted with caution, and that MIC testing is the most reliable technique for differentiating these two resistance patterns in Staphylococcus aureus.