Mitotic instability was found in an intraspecific hybrid of Haplopappus gracilis (Nutt.) Gray and in an interspecific hybrid of H. arenarius Benth. and H. aureus Gray. The latter cross was between distantly related species with different chromosome numbers and amounts of DNA. The intraspecific hybrid exhibited a partly recessive phenotype due to loss of a chromosome segment containing the wild type locus, and the interspecific hybrid showed abnormal developmental patterns for several morphological characters due to chromatin loss. Both hybrids were slower growing, smaller, and generally weaker than parental types. In both examples, this weakness was correlated with chromatin loss due to cleavage by cell wall formation across chromosome arms too long to separate properly at anaphase. This was caused by a very unequal translocation in H. gracilis and to a disparity in genome sizes in the interspecific hybrid. In both examples, the initial chromosome cleavage resulted in a breakage‐fusion‐bridge cycle that persisted into some BC, progeny of H. gracilis.