Since 1981, 21 children diagnosed with mixed connective tissue disease (MCTD) have been reported in detail in the literature in Japan. Overlapping clinical features and laboratory findings of these children were analyzed according to the established criteria of the Ministry of Health and Welfare, Japan. Mixed connective tissue disease in childhood typically begins with Raynaud's phenomenon preceded by several months or years with the appearance of other symptoms and signs including fever, arthralgia, myalgia, and/or progressive systemic sclerosis like skin manifestations. Serologically all the children with MCTD were positive for anti-ribonuclear protein (RNP) antibody with speckled-type antinuclear antibody. Hypergammaglobulinemia, positive rheumatoid factor, and normocomplementemia were characteristic. In general, prognosis is considered to be fairly good as opposed to systemic lupus erythematosus in childhood, but severe pericarditis/myocarditis or nephrotic syndrome can occur. Long-term follow-up study and improved laboratory detection of anti-ribonucleoprotein antibodies will be necessary for further characterization of MCTD in childhood, and for the improvement of therapy.