AbstractWe study the self-similar blow-up profiles associated to the following second-order reaction-diffusion equation with strong weighted reaction and unbounded weight:\partial_{t}u=\partial_{xx}(u^{m})+|x|^{\sigma}u^{p},posed for {x\in\mathbb{R}}, {t\geq 0}, where {m>1}, {0<p<1} and {\sigma>\frac{2(1-p)}{m-1}}. As a first outcome, we show that finite time blow-up solutions in self-similar form exist for {m+p>2} and σ in the considered range, a fact that is completely new: in the already studied reaction-diffusion equation without weights there is no finite time blow-up when {p<1}. We moreover prove that, if the condition {m+p>2} is fulfilled, all the self-similar blow-up profiles are compactly supported and there exist two different interface behaviors for solutions of the equation, corresponding to two different interface equations. We classify the self-similar blow-up profiles having both types of interfaces and show that in some cases global blow-up occurs, and in some other cases finite time blow-up occurs only at space infinity. We also show that there is no self-similar solution if {m+p<2}, while the critical range {m+p=2} with {\sigma>2} is postponed to a different work due to significant technical differences.