A cross-sectional study was conducted in Hawassa town and its surroundings from October 2007 to May 2008 to estimate the prevalence of bovine tuberculosis (BTB) based on comparative interadermal tuberculin test (CIDT) and abattoir survey. Accordingly, 39 herds comprising 413 cattle were subjected to CIDT, and the herd and individual animal prevalence were 48.7% (19/39) and 11.6% (48/413), respectively. One of the 16 milk samples collected from tuberculin-positive cows was culture positive. The prevalence significantly differed among the age group (P = 0.001) and management system (P = 0.001). Thus, age group over four (OR = 7.9) and animal with poor management system (OR = 4.1) had a higher odds for tuberculin reactivity compared to those with age group under four and cattle with good management system, respectively. Of the total 1,023 cattle subjected to postmortem examination, 11 (1.1%) were found to be positive for gross tuberculous lesions. Larger proportion (50%) of TB lesion was recorded in the respiratory pathway followed by digestive system (28.6%) and prescapular lymph nodes (21.4%). Of 14 tissue specimens collected from the gross lesions, four (28.6%) were positive for histopathological TB lesions. In conclusion, this study revealed the importance of BTB in the study area in particular and the region in general.