Smallest in a large way! (5)
I believe the answer is:
least
'smallest' is the definition.
(synonyms)
'in a large way' is the wordplay.
'in' is an insertion indicator.
'a large' becomes 'leat' (I can't explain this - if you can you should give a lot more credence to this answer).
'way' becomes 's' (Compass direction - South).
'leat' placed around 's' is 'LEAST'.
Can you help me to learn more?
(Other definitions for least that I've seen before include "Most insignificant" , "Superlative form of 'little'" , "Of minimal significance" , "Bottom" , "Being lowest in importance - gone stale" .)