The vast majority of microbes are unculturable and thus cannot be sequenced by means of traditional methods. High-throughput sequencing techniques like 454 or Solexa-Illumina make it possible to explore those microbes by studying whole natural microbial communities and analysing their biological diversity as well as the underlying metabolic pathways. Over the past few years, different methods have been developed for the taxonomic and functional characterization of metagenomic shotgun sequences. However, the taxonomic classification of metagenomic sequences from novel species without close homologue in the biological sequence databases poses a challenge due to the high number of wrong taxonomic predictions on lower taxonomic ranks. Here we present CARMA3, a new method for the taxonomic classification of assembled and unassembled metagenomic sequences that has been adapted to work with both BLAST and HMMER3 homology searches. We show that our method makes fewer wrong taxonomic predictions (at the same sensitivity) than other BLAST-based methods. CARMA3 is freely accessible via the web application WebCARMA from http://webcarma.cebitec.uni-bielefeld.de.