Two concepts, (1) companies are ‘living’ entities and (2) ‘company ecology’, stimulated our hypothesis that towns are ‘enterprise ecosystems’. This hypothesis cannot be tested directly. However, if it is correct, application of clustering and ordination techniques used frequently in studies of natural ecosystems, should reveal clusters of towns that are statistically significantly different (p < 0.05). A dataset of 47 towns in the Karoo, South Africa served as study material and their enterprise assemblages were profiled through the use of a simple method based on the examination of telephone directories. Clustering and ordination techniques revealed six different clusters of towns at a correlation coefficient level of 0.65 and the clusters differed significantly (p < 0.05) in some respects. The agricultural products and services, the tourism and hospitality, and the trade sectors were particularly important in defining these clusters. We concluded that enterprise ecology is a valid concept and towns are ‘ecosystems’ that also cluster together in larger groupings. An array of potentially important techniques and approaches for the study of business development in towns now provide support to, and intriguing questions confront, academic and practical researchers of enterprise development in towns.