The diagnostic accuracy of 4 approaches to interpreting neuropsychological test results are evaluated in 672 cognitively normal and 407 cognitively impaired persons using the Mayo Cognitive Factor Scales (G. E. Smith et al., 1994). The interpretation approaches studied are absolute scores, difference scores, profile variability, and change scores at 1- to 2-year test-retest intervals. All dependent measures were "highly significant" when diagnostic groups were compared on null hypothesis significance testing analyses. In contrast, varied accuracy rates were obtained when each measure's ability to correctly classify individuals was evaluated relative to overall diagnostic accuracy. Odds ratios were also highly varied and ranged from < or = 1.0 (i.e., chance) to 34.9. The clinical usefulness of absolute scores and difference scores in data interpretation is supported. Neither profile variability measures nor measures of change over time were diagnostically useful.