Fluorescence in situ hybridization (FISH) allows visualization of chromosomes and genes in interphase nuclei. Dual labeling FISH with probes for a gene of interest and the corresponding centromere can be used to determine chromosomal deletion and gene amplification. In case of a deletion less gene signals than centromere signals are found. In case of amplification gene signal number is distinctly increased as compared to centromere signals. To study gene amplification in fresh and formalin fixed bladder cancer we used gene specific probes for erbB-2, EGF-r, and 11q13 (bcl-1, PRAD1) together with their corresponding centromere probes p17H8, p7alphaTET and plC11A. Amplification was seen in 10/140 tumors for erbB-2, in 5/107 tumors for EGF-r, and in 15/137 tumors for 11q13. Different patterns of amplification suggested that FISH allows distinction of intrachromosomal (amplified genes in clusters) and extrachromosomal amplification (diffuse distribution of signals).