Tools for multiple sequence alignments such as ClustalW (Thompson et al., 1994) are readily available and thus, structure prediction from an alignment is a tempting approach [e.g. RNAalifold (Hofacker et al., 2002) ]. Such methods heavily depend on the sequence conservation and quality of the underlying alignment. However, ncRNAs are conserved rather on the structure level than on the sequence level. The gold standard of RNA comparative structure prediction is the Sankoff approach as it does not rely on a high-quality sequence alignment and captures the structural conservation of ncRNAs. Sankoff (1985) introduced a theoretical dynamic programming algorithm for simultaneous folding and aligning for a set of N sequences that takes O(n 3N ) time and O(n 2N ) space. Practical variants have been derived which more or less retain the Sankoff principle by sacrificing optimality. Alignment-free methods aim to avoid the pragmatic restrictions made in a practical Sankoff approach as well as the reliance on a high-quality alignment [e.g. CARNAC (Perriquet et al., 2003) ]. Note that all of these comparative structure prediction methods exclude the prediction of RNA pseudoknots.