Tumor specimens of 203 infants with neuroblastomas of different clinical stages-registered in successive multicenter clinical trials of the German Society of Pediatric Oncology-could be examined for N-myc amplification, chromosome 1-ploidy and-structure, CD44 std. expression (in tumor tissue, and also in patient's sera). Eighty-seven (= 43%) of these infants had a non-localized, disseminated neuroblastoma, mainly involving sympathetic nerve tissue, lymph nodes, liver, skin, bone marrow and bones (46 patients were classified into the 4 group, 41 patients in the true 4 group). If the clinical classification between stage 4 and stage 4s was neglected, then 17 of these infants (= 20%) had N-myc amplification (4-64 copies) with 16 already dead. Seven of 9 examined patients with true stage 4- had chromosome 1p aberrations (with N-myc amplification in 5), and among the dead there were 2 with CD44 negative expression. In another series, serum CD44 std. was measured by ELISA, and the highest (significantly different) Kruskal-Wallis mean rank values (147.8) were found in infants (n = 6) with stage 4s compared to the low mean-rank-value of 71.9 in patients with stage 4 (n = 65). Stage 1-3 patients (n = 42) had values of 99.8-88.6. Thus, infants with disseminated neuroblastomas, showing non-diploidy, normal chromosome 1p structure, non-N-myc amplification and high CD44 std. expression in tumor tissue, and also high CD44 std. values in serum, will have the highest chance of survival due to tumor-non-progression. On the other hand, N-myc amplification in the tumor cells was found to be characteristic for stage 4s neuroblastoma patients with tumor progression (n = 6). Therefore, 4s neuroblastoma-patients with N-myc amplified tumors should be aggressively treated like true stage 4 tumor patients.