Expressed sequences (e.g. ESTs) are a strong source of evidence to improve gene structures and predict reliable alternative splicing events. When a genome assembly is available, ESTs are suitable to generate gene-oriented clusters through the well-established EasyCluster software. Nowadays, EST-like sequences can be massively produced using Next Generation Sequencing (NGS) technologies. In order to handle genome-scale transcriptome data, we present here EasyCluster2, a reimplementation of EasyCluster able to speed up the creation of gene-oriented clusters and facilitate downstream analyses as the assembly of full-length transcripts and the detection of splicing isoforms.