Introduction Coagulase-negative staphylococci are considered as microorganisms with little virulence and usually as contaminants. In order to establish the role of Staphylococcus epidermidis as a pathogen in diabetic foot osteomyelitis, in addition to the isolation of the sole bacterium from the bone it will be necessary to demonstrate the histopathological changes caused by the infection. Methods A consecutive series of 222 diabetic patients with foot osteomyelitis treated surgically in the Diabetic Foot Unit at La Paloma Hospital (Las Palmas de Gran Canaria, Canary Islands, Spain) between 1 October 2002 and 31 October 2008. From the entire series including 213 bone cultures with 241 isolated organisms, we have analyzed only the 139 cases where Staphylococci were found. We analyzed several variables between the two groups: Staphylococcus aureus versus Staphylococcus epidermidis. Results Of the 134 patients included in this study, Staphlylococcus epidermidis was found as the sole bacterium isolated in 11 cases and accompanied by other bacteria in 12 cases. Staphlylococcus aureus was found as the sole bacterium isolated in 72 cases and accompanied by other bacteria in 39 cases. Histopathological changes were found in the cases of osteomyelitis where Staphylococcus epidermidis was the sole bacterium isolated. Acute osteomyelitis was found to a lesser extent when Staphylococcus epidermidis was the sole bacterium isolated but without significant differences with the cases where Staphylococcus aureus was the sole bacterium isolated. Conclusion Staphylococcus epidermidis should be considered as a real pathogen, not only a contaminant, in diabetic patients with foot osteomyelitis when the bacterium is isolated from the bone. No differences in the outcomes of surgical treatment have been found with cases which Staphlylococcus aureus was isolated.