Since its introduction, there has been a debate about the validity of the factorial structure of the SCL-90-R. In this study we investigate whether the lack of agreement with respect to the dimensionality can be partly explained by important variables that might differ between samples such as level of psychological distress, the variance of the SCL-90-R scores and sex. Three samples were included: a sample of severely psychiatrically disturbed patients (n=3078), a sample of persons with Gender Incongruence (GI; n=410) and a sample of depressed patients (n=223). A unidimensional pattern of findings were found for the GI sample. For the severely disturbed and depressed sample, a multidimensional pattern was found. In the depressed sample sex differences were found in dimensionality: we found a unidimensional pattern for the females, and a multidimensional one for the males. Our analyses suggest that previously reported conflicting findings with regard to the dimensional structure of the SCL-90-R may be due to at least two factors: (a) level of self-reported distress, and (b) sex. Subscale scores should be used with care in patient groups with low self-reported level of distress.