Cocaine dependence (CD) is a multifactorial disorder, variable in its manifestations, and heritable. We examined the concurrent validity of homogeneous subgroups of CD as phenotypes for genetic analysis. We applied data reduction methods and an empirical cluster-analytic approach to measures of cocaine use, cocaine-related effects, and cocaine treatment history in 1393 subjects, from 660 small nuclear families. Four of the six clusters that were derived yielded heritability estimates in excess of 0.3. Linkage analysis showed genome-wide significant results for two of the clusters. Here we examine the concurrent validity of the six clusters using a variety of demographic and substance-related measures. In addition to being differentiated by a variety of cocaine-related measures, the clusters differed significantly on measures that were independent of those used to generate the clusters, i.e., demographic features and prevalence rates of co-morbid substance use and psychiatric disorders. These findings support the validity of the methods used to derive homogeneous subgroups of CD subjects and the resulting CD subtypes. Independent replication of these findings would provide further validation of this approach.