We report two carriers of Xp21 muscular dystrophy with unusual clinical manifestations and striking variability of dystrophin deficiency within the same muscle biopsy. The first patient was a 60-year-old nun with recent onset of cramps and proximal weakness, mimicking an acquired myopathy. Muscle biopsy disclosed slight alterations in one sample and severe dystrophic changes in another; dystrophin was absent in 7% fibers in the former specimen and in 60% in the second. X inactivation was skewed with 90% cells inactivating the same X chromosome. The second patient was a 17-year-old girl with hyperCKemia, learning disability and a family history of X-linked muscular dystrophy. Muscle biopsy displayed slight fiber size variability and some internal nuclei; dystrophin was absent only in one muscle fiber. A second sample with the same morphological features demonstrated dystrophin deficiency with mosaic distribution. The pattern of X inactivation was normal. These cases emphasize the variability of histopathological changes and dystrophin deficiency in Xp21 muscular dystrophy carriers and the risk of sampling errors in muscle biopsy.