Phylogenomic studies have improved understanding of deep metazoan phylogeny and show promise for resolving incongruences among analyses based on limited numbers of loci. One region of the animal tree that has been especially difficult to resolve, even with phylogenomic approaches, is relationships within Lophotrochozoa (the animal clade that includes molluscs, annelids, and flatworms among others). Lack of resolution in phylogenomic analyses could be due to insufficient phylogenetic signal, limitations in taxon and/or gene sampling, or systematic error. Here, we investigated why lophotrochozoan phylogeny has been such a difficult question to answer by identifying and reducing sources of systematic error. We supplemented existing data with 32 new transcriptomes spanning the diversity of Lophotrochozoa and constructed a new set of Lophotrochozoa-specific core orthologs. Of these, 638 orthologous groups (OGs) passed strict screening for paralogy using a tree-based approach. In order to reduce possible sources of systematic error, we calculated branch-length heterogeneity, evolutionary rate, percent missing data, compositional bias, and saturation for each OG and analyzed increasingly stricter subsets of only the most stringent (best) OGs for these five variables. Principal component analysis of the values for each factor examined for each OG revealed that compositional heterogeneity and average patristic distance contributed most to the variance observed along the first principal component while branch-length heterogeneity and, to a lesser extent, saturation contributed most to the variance observed along the second. Missing data did not strongly contribute to either.Additional sensitivity analyses examined effects of removing taxa with heterogeneous branch lengths, large amounts of missing data, and compositional heterogeneity. Although our analyses do at University of Oslo Library on September 26, 2016 http://sysbio.oxfordjournals.org/ Downloaded from 3 not unambiguously resolve lophotrochozoan phylogeny, we advance the field by reducing the list of viable hypotheses. Moreover, our systematic approach for dissection of phylogenomic data can be applied to explore sources of incongruence and poor support in any phylogenomic dataset.Keywords: Trochozoa, Spiralia, Mollusca, Nemertea, Annelida, Brachiopoda, Phoronida, Entoprocta, Platyzoa, Polyzoa, Bryozoa Understanding of deep phylogeny has improved with the application of phylogenomic approaches (e.g., Philippe et al. 2004Philippe et al. , 2005Matus et al. 2006; Delsuc et al. 2006; Dunn et al. 2008; Hejnol et al. 2009; Kocot et al. 2011;Smith et al. 2011;Struck et al. 2011;Zhong et al. 2011a;Ryan et al. 2013;Moroz et al. 2014, Torruella et al. 2015, Whelan et al. 2015.Nonetheless, some regions of the tree of life with short internodes, probably due to rapid diversification, still lack resolution. Relationships within Lophotrochozoa (Halanych et al. 1995) are one such example. Lophotrochozoa is a well-supported clade of invertebrates that includes Anneli...