As the underground market of malware flourishes, there is an exponential increase in the number and diversity of malware. A crucial question in malware analysis research is how to define malware specifications or signatures that faithfully describe similar malicious intent and clearly stand out from other programs. It is evident that the classical syntactic signatures are insufficient to defeat state-of-the art malware. Behavior-based specifications which capture real malicious characteristics during runtime, have become more prevalent in anti-malware tasks, such as malware detection and malware clustering. This kind of specification is typically extracted from system call dependence graphs that a malware sample invokes. In this paper we present replacement attacks to poison behavior-based specifications by concealing similar behaviors among malware variants. The essence of the attacks is to replace a behavior specification to its semantically equivalent one, so that similar malware variants within one family turn out to be different. As a result, malware analysts have to put more efforts to re-analyze similar samples. We distill general attacking strategies by mining more than 5,000 malware samples’ behavior specifications and implement a compiler-level prototype to automate replacement attacks. Experiments on 960 real malware samples demonstrate effectiveness of our approach to impede multiple malware analyses based on behavior specifications, such as similarity comparison and malware clustering. In the end, we provide possible counter-measures to strengthen behavior-based malware analysis.