Tissue-associated bacterial community profiles generated using a nested polymerase chain reaction–denaturing gradient gel electrophoresis (DGGE) approach and culture-dependent and culture-independent isolation techniques were compared. Oyster samples were collected from 2 harvest areas along the coast of Maine, in the United States. Profiles from both isolation strategies were evaluated using Sorensen’s index of similarity and cluster analysis of gel banding patterns. Culture independent profiles were further evaluated using the Shannon diversity index. In general, the culture-dependent strategy resulted in a greater number of bands within a profile. Bacterial DGGE profiles were found to be highly similar within an isolation strategy, with a higher degree of unrelatedness between culture-dependent and -independent techniques. Cluster analysis identified bands present in the culture-dependent strategy and not the total DNA technique, and vice versa. Significant differences in community profiles between oyster-associated and seawater were observed, indicating a diverse group of specialist bacterial species inhabit and are able to proliferate within the oyster.