OBJECTIVES Several ABILHAND Rasch-built manual ability scales were previously developed for chronic stroke (CS), cerebral palsy (CP), rheumatoid arthritis (RA), systemic sclerosis (SSc) and neuromuscular disorders (NMD). The present study aimed to explore the applicability of a generic manual ability scale unbiased by diagnosis and to study the nature of manual ability across diagnoses. DESIGN Cross-sectional study. SETTING Outpatient clinic homes (CS, CP, RA), specialised centres (CP), reference centres (CP, NMD) and university hospitals (SSc). PARTICIPANTS 762 patients from six diagnostic groups: 103 CS adults, 113 CP children, 112 RA adults, 156 SSc adults, 124 NMD children and 124 NMD adults. PRIMARY AND SECONDARY OUTCOME MEASURES Manual ability as measured by the ABILHAND disease-specific questionnaires, diagnosis and nature (ie, uni-manual or bi-manual involvement and proximal or distal joints involvement) of the ABILHAND manual activities. RESULTS The difficulties of most manual activities were diagnosis dependent. A principal component analysis highlighted that 57% of the variance in the item difficulty between diagnoses was explained by the symmetric or asymmetric nature of the disorders. A generic scale was constructed, from a metric point of view, with 11 items sharing a common difficulty among diagnoses and 41 items displaying a category-specific location (asymmetric: CS, CP; and symmetric: RA, SSc, NMD). This generic scale showed that CP and NMD children had significantly less manual ability than RA patients, who had significantly less manual ability than CS, SSc and NMD adults. However, the generic scale was less discriminative and responsive to small deficits than disease-specific instruments. CONCLUSIONS Our finding that most of the manual item difficulties were disease-dependent emphasises the danger of using generic scales without prior investigation of item invariance across diagnostic groups. Nevertheless, a generic manual ability scale could be developed by adjusting and accounting for activities perceived differently in various disorders.