Spontaneous mitotic recombination occurs in response to DNA damage incurred during DNA replication or from lesions that do not block replication but leave recombinogenic substrates such as single-stranded DNA gaps. Other types of damages result in general genome instability such as chromosome loss, chromosome fragmentation, and chromosome rearrangements. The genome is kept intact through recombination, repair, replication, checkpoints, and chromosome organization functions. Therefore when these pathways malfunction, genomic instabilities occur. Here we outline some general strategies to monitor a subset of the genomic instabilities: spontaneous mitotic recombination and chromosome loss, in both haploid and diploid cells. The assays, while not inclusive of all genome instability assays, give a broad assessment of general genome damage or inability to repair damage in various genetic backgrounds.