TOPD/FMTS is a new software for comparing phylogenetic trees. It has been developed to calculate the differences between trees. The software implements several previously described methods and new algorithms for comparing phylogenetic trees. It combines the TOPD program (TOPological Distance), which compares two trees with the same taxa or two pruned trees, and the FMTS program (From Multiple To Single), which converts multi-gene family trees to single-gene trees. This second program is activated automatically only if one or both trees to be compared are multi-gene family trees. Both programs have several parameters that can be modified. The TOPD program compares trees with several methods that this software calls Nodal, Split, Quartets &Triplets, quickquartest, duplidist and Disagree. Each option of this software is also complemented with a random analysis to test the null hypothesis that any comparison is not better than random.