The purpose of this study was to evaluate the variability of cystosonographic bladder tumor measurements with both operator and bladder volume changes. Ten dogs with bladder tumors were included. In each dog, three operators determined tumor dimensions for three different bladder volumes. Intraclass correlation coefficient was used to assess operator reliability. Response Evaluation Criteria in Solid Tumors (RECIST) and greater than or equal to 50% differences in tumor measurements were used as guidelines. Poor to fair correlations between operators were found for the different tumor dimensions (r(I) = 0.4 - 0.7). The percent differences in tumor dimensions with operator and bladder volume changes were significant enough to misclassify the tumors into the categories of partial response (PR) or progressive disease (PD). These results suggest that cystosonographic measurements of bladder tumors are affected by both changes in operator and bladder volume, and the discrepancies are significant enough to change response classification.