The Iron have not lost in nine games and face an AFC Wimbledon side who beat them earlier this season, while second-placed Burton Albion will look to recover from FA Cup defeat
Sacking Brian Laws in November may prove the turning point in Scunthorpe's season, with the manager removed after an FA Cup loss to rivals Grimsby Town.
Laws' assistant - Russ Wilcox - was appointed on a caretaker basis and quickly hired full-time after a stunning start to life in the top job.
Under Wilcox, Scunthorpe have won seven and drawn two in League Two, form that has seen them rise to the top of the table.
They have also splashed the cash in the January transfer window, signing Yeovil Town striker Paddy Madden, while fellow forwards Paul Hayes and Gary McSheffrey have also joined the club.
Where that puts the division's top scorer Sam Winnall - who has scored 13 goals in 24 League Two matches - remains to be seen, but Wilcox certainly has an embarrassment of riches in the attacking department.
AFC Wimbledon lie 15th in the table, with just one win in their last nine matches, but they will take heart from their 3-2 win over Scunthorpe in August.
On that occasion, Michael Smith, Harry Pell and Chris Arthur scored in the last 30 minutes as they came from two goals down to claim a terrific victory.
Just one point behind Scunthorpe are Burton Albion, who lost their first match in 12 on Tuesday, slumping to a 4-1 FA Cup third round replay defeat against Bournemouth of the Championship.
Billy Kee and Adam McGurk have struck up a fine partnership up front for Burton this season, and their next test comes at struggling Bury on Saturday.
Third-placed Chesterfield, meanwhile, face a tough trip to Southend United, who are just two places below them.
Still riding high after their shock FA Cup win over Leeds United, Rochdale welcome the visit of Plymouth Argyle, while other sides in the play-off spots - Fleetwood Town and Oxford United - take on Hartlepool United and Wycombe Wanders respectively.
At the wrong end of the table, rock-bottom Northampton Town visit the side just one place above them, Torquay United, in a crucial relegation battle.
James Beattie's Accrington Stanley hit the road to face Cheltenham Town, and the resurgent York City host Bristol Rovers, looking for their fourth win in a row.
Other fixtures on Saturday see Exeter City meet Morecambe, Newport County battle Dagenham and Redbridge, and Portsmouth host Mansfield Town.