In the present study, we analyze the nature of TP53 intron 1 rearrangements, screen the to date largest collection of OS and other tumor types for such rearrangements, describe the identification of a TP53 intron 1 disrupting germline inversion in a four generation LFS family and characterize this locus and TP53 activity in tumors of this family. The gene discussed is TP53; the disease is neoplasm.