FastTree is a method for constructing large phylogenies and estimating their reliability, designed to handle alignments with over 10,000 sequences. Unlike traditional methods that store a distance matrix, FastTree stores sequence profiles of internal nodes, which are used to implement Neighbor-Joining and heuristics to identify candidate joins. FastTree then uses nearest neighbor interchanges to reduce the tree length. This approach significantly reduces the space and time complexity compared to storing a distance matrix. FastTree also uses local bootstrapping to estimate the reliability of the tree, which is much faster than traditional bootstrapping. In simulations and real alignments, FastTree is more accurate and faster than other methods, and it scales well to large alignments. The method is particularly useful for analyzing large gene families and for applications in taxonomy, gene function prediction, and environmental DNA classification.FastTree is a method for constructing large phylogenies and estimating their reliability, designed to handle alignments with over 10,000 sequences. Unlike traditional methods that store a distance matrix, FastTree stores sequence profiles of internal nodes, which are used to implement Neighbor-Joining and heuristics to identify candidate joins. FastTree then uses nearest neighbor interchanges to reduce the tree length. This approach significantly reduces the space and time complexity compared to storing a distance matrix. FastTree also uses local bootstrapping to estimate the reliability of the tree, which is much faster than traditional bootstrapping. In simulations and real alignments, FastTree is more accurate and faster than other methods, and it scales well to large alignments. The method is particularly useful for analyzing large gene families and for applications in taxonomy, gene function prediction, and environmental DNA classification.