A method for enriching a target sequence in a reaction mixture, said method comprising: a. subjecting a reaction mixture suspected of having a target sequence duplex and a reference sequence duplex to a first denaturing temperature that is above the melting temperature (T m) of the reference sequence duplex and the target sequence duplex so as to permit the denaturation of said target sequence duplex and said reference sequence duplex, wherein said target sequence duplex comprises one or more insertion, deletion or alteration and differ by at least one nucleotide from said reference sequence duplex, and wherein said target sequence is at least 50% homologous to said reference sequence duplex and is amplifiable by the same primer pair as said reference sequence duplex and wherein the target sequence is less prevalent in the reaction mixture than the reference sequence; b. reducing the temperature of the reaction mixture to a hybridization temperature so as to permit formation of target strand/reference strand duplexes and prevent binding of said primer pair to the denatured target and reference strands in the reaction mixture, wherein the hybridization temperature is below the critical temperature (Tc) and above the primer annealing temperature; c. increasing said amplification reaction mixture to a critical temperature (Tc) that is below the T m of said reference sequence duplex so as to permit the preferential denaturation of said duplexes of step (b) to form denatured target and reference strands; d. reducing the temperature of the reaction mixture to a primer annealing temperature so as to permit said primer pair to anneal to said target and reference strands; and e. extending said primer pair so as to enrich said target sequence relative to said reference sequence; wherein the method is repeated for two or more cycles. a. subjecting a reaction mixture suspected of having a target sequence duplex and a reference sequence duplex to a first denaturing temperature that is above the melting temperature (T m) of the reference sequence duplex and the target sequence duplex so as to permit the denaturation of said target sequence duplex and said reference sequence duplex, wherein said target sequence duplex comprises one or more insertion, deletion or alteration and differ by at least one nucleotide from said reference sequence duplex, and wherein said target sequence is at least 50% homologous to said reference sequence duplex and is amplifiable by the same primer pair as said reference sequence duplex and wherein the target sequence is less prevalent in the reaction mixture than the reference sequence; b. reducing the temperature of the reaction mixture to a hybridization temperature so as to permit formation of target strand/reference strand duplexes and prevent binding of said primer pair to the denatured target and reference strands in the reaction mixture, wherein the hybridization temperature is below the critical temperature (Tc) and above the primer annealing temperature; c. increasing said amplification reaction mixture to a critical temperature (Tc) that is below the T m of said reference sequence duplex so as to permit the preferential denaturation of said duplexes of step (b) to form denatured target and reference strands; d. reducing the temperature of the reaction mixture to a primer annealing temperature so as to permit said primer pair to anneal to said target and reference strands; and e. extending said primer pair so as to enrich said target sequence relative to said reference sequence;