SummaryIn recent years, because of the security requirements of resource‐constrained devices, design and analysis of lightweight block ciphers has received more attention. mCrypton is a lightweight block cipher that has been specifically designed for using in resource‐constrained devices, such as low‐cost radio‐frequency identification tags and sensors. In this paper, we consider cryptanalysis of full‐round mCrypton‐64 using a new extension of biclique attack called non‐isomorphic biclique cryptanalysis. As it is known, effectiveness of the biclique attack is highly dependent to the weakness of key schedule, and it does not seem to be appropriate for block ciphers with strong key scheduling. The non‐isomorphic biclique attack, using an asymmetric key partitioning technique, provides more degrees of freedom to the attacker and makes it possible to use the diffusion layer properties of a block cipher for constructing longer bicliques. Results show that the attack on full‐round mCrypton requires 233.9 chosen plaintexts and a time complexity of 262.67 encryptions. The computational complexity reduces to 262.3, 261.4, and 259.75 encryptions for 10, 8, and 6 rounds of mCrypton‐64, respectively. We also have a discussion on the general form of the computational complexity for non‐isomorphic biclique cryptanalysis. Copyright © 2014 John Wiley & Sons, Ltd.