There have been proposals to expand definitions for categorical disorders and dimensionally-conceptualized syndromes (e.g., psychopathy) to include negative mood lability and dysregulation (NMD). Factor analytic results are often presented in support of these proposals, and we provide factor analytic demonstrations across clinically-oriented samples showing that NMD indicators load strongly onto factors with a range of psychopathology. This is unsurprising from a transdiagnostic perspective but shows that factor analysis could potentially be used to justify expanding definitions for specific constructs even though NMD indicators show strong, nonspecific loadings on other psychopathology factors ranging widely in nature. Expanding construct definitions and assessment approaches to emphasize NMD also may negatively impact discriminant validity. Acknowledging differing viewpoints on expanding construct definitions, we agree that targeting NMD is essential for comprehensive assessment. We use our analytic demonstrations to discuss model interpretation and balancing comprehensiveness with specificity when assessing NMD across traditional categorical and transdiagnostic frameworks.