The histochemical and ultrastructural analysis of the nuclear components involved in RNA transcription and splicing can reveal the occurrence of cellular dysfunctions eventually related to the onset of a pathological phenotype. In recent years, nuclear histochemistry at light and electron microscopy has increasingly been used to investigate the basic mechanisms of skeletal muscle diseases; the study in situ of nuclei of myofibres and satellite cells proved to be crucial for understanding the pathogenesis of skeletal muscle wasting in sarcopenia, myotonic dystrophy and laminopathies.