In Southern Italy, buffalo (Bubalus bubalis) milk is mostly intended for the manufacture of Mozzarella di Bufala Campana Protected Denomination of Origin (PDO) cheese. Despite the economic boost of the last 2 decades, the buffalo farming system should be improved to maximize the efficiency of the dairy industry, improve yield and quality of milk and cheese, and work toward better animal welfare. Milk somatic cell count (SCC) is used worldwide as an indicator of udder health in individual milk and is useful for monitoring farm hygiene in bulk milk. Mastitis data are currently not available on a large scale in Italy; thus, SCC is essential for identifying animals with suspected udder infection and inflammation. Moreover, high milk SCC is associated with altered composition and acidity, and poor technological properties of milk. However, payment systems of the PDO area are based simply on the delivered volume of milk rather than on quality characteristics. Hence, currently there are no penalties for elevated SCC in bulk milk in the Italian buffalo dairy industry. In addition, SCC for buffalo milk is not mentioned by either the European Community regulations or the PDO protocol, evidencing a lack of rules for the maximum SCC limit. To provide a phenotypic characterization of SCC at the population level and to improve knowledge on buffalo milk quality, 876,299 test-day records of 70,156 buffaloes reared in the PDO area were analyzed. Data revealed that around 11% of herd-test-dates (≥5 animals sampled each) showed average milk SCC ≥400,000 cells/mL (i.e., above the threshold fixed by the European Community for bovine milk). This suggests that there is room to improve SCC at both the farm and individual level. Within first parity, more than 28 and 15% of lactations had average SCC ≥200,000 and ≥300,000 cells/mL, respectively. Both percentages increased with parity and were 39 and 25% in sixth parity, respectively. Supporting this, the proportion of lactations with average SCC ≥500,000 cells/mL increased from 6% in first parity to 12% in sixth parity. Milk yield and SCC were negatively correlated with each other, especially when SCC level was high. An ANOVA was carried out on test-day record milk yield and composition traits, with fixed effects of parity, lactation stage, class of somatic cell score (n = 6), month of calving, and their interactions; buffalo, herd-test-date, and residual were considered random effects. Significantly lower milk yield and lactose percentage were estimated in progressively higher classes of somatic cell score, whereas no significant differences were observed for fat and protein percentages. This is the first attempt to investigate milk SCC in a large data set of Italian dairy buffaloes. These findings may be helpful for defining reliable and effective SCC thresholds to be adopted whenever specific penalties for high SCC are included in milk payment systems. Finally, these results could be used in mastitis monitoring plans aiming to reduce SCC and udder issues at both the individual and farm levels in the Italian buffalo population.